Metastasis from one tumor to another

Tumour in tumour metastasis. The occurrence of more than one primary tumour in the same person is uncommon, nevertheless metastasis of one tumour to another is an extraordinary event. The malignant tumour usually metastasizes in a benign tumour, however a metastatic deposit within a malignant tumour is described. In the present study the literature is briefly reviewed and 43 new cases are described: in 38 the host neoplasm is a benign one, and in 4 is a malignant tumour. In the last case the metastases are present both in a malignant and in a benign tumor.     

Tumour versus patient: vascular and tumour survival versus prognosis

The concept that malignant solid tumour growth depends on angiogenesis is widely recognized. For some tumour types, there is a measurable range of vascularity and the link between prognosis and increased vascular density, best observed at the hotspots at the edge, is now established. What is less discussed are the corollaries: that tumour invasion requires tissue destruction; that the neovasculature must be not only protected but also sustained, especially at the tumour edge; that for tumour survival the edge is the future and the centre is history; and that angiogenesis is essential not only for tumour growth but also for tumour invasion. Different patterns of vascular density in tumour edge and centre have been observed, and these are linked to lymphatic spread and prognosis. The variation is attributable to differing interactions between endothelium and the tumour cell that dictate vascular and tumour survival; this may become relevant to anti-angiogenesis therapies.     

Cytokeratin expression and epithelial differentiation in Warthin's tumour and its metaplastic (infarcted) variant

AIMS: Warthin's tumour is characterized by a bilayered columnar epithelium. Transformation into metaplastic (infarcted) Warthin's tumour includes squamous metaplasia of the epithelium along with regressive changes in the stroma. Misinterpretation of metaplastic Warthin's tumour for malignancy is a serious diagnostic pitfall. This study assesses the utility of cytokeratin expression in Warthin's tumour and its metaplastic variant. METHODS AND RESULTS: Twenty-six cases of Warthin's tumour, among them eight metaplastic Warthin's tumours, were investigated employing immunohistochemistry. Both Warthin's tumour and its metaplastic variant regularly expressed cytokeratins (CK) 7, 8, 18, and 19. Staining results with antibodies to CK10, 10/13, 1/2/10/11, and 20 were negative in all specimens. Immunoreactivity for CK 5/14 and 17 was restricted to basal cells in Warthin's tumour, but involved basal as well as surface cells in metaplastic Warthin's tumour. CONCLUSIONS: Warthin's tumour and its metaplastic (infarcted) variant both express CK 7, 8, 18, and 19, which are typical for columnar differentiation. Cytokeratins typical of squamous differentiation are absent from Warthin's tumour and its metaplastic variant, irrespective of the squamous morphology of the epithelium in metaplastic Warthin's tumour. The expression of CK 5/14 and 17, which are typical of regenerative cells, is restricted to basal cells in Warthin's tumour, but is expressed also in surface cells in metaplastic Warthin's tumour.     

Polymorphonuclear cells stimulate the migration and metastatic potential of rat sarcoma cells

The tumour microenvironment, which is largely composed of inflammatory cells, is a crucial participant in the neoplastic process through the promotion of cell proliferation, survival and migration. Neutrophil polymorphonuclear cells (PMNs) induce inflammatory reactions that can be either cytotoxic for tumour cells or can promote tumour growth and metastasis. Previously, we have reported a spontaneous metastasis tumour model that has tumour PMNs infiltration, and metastasis, to liver and spleen. The aim of this study was to evaluate the PMNs influences on the tumour cell invasion and metastatic properties. We analysed intercellular adhesion molecule-1 (ICAM-1), urokinase-type plasminogen activator receptor (uPAR), MT1-MMP (membrane type 1-matrix metalloproteinase) and MMP2 protein expression in TuE-t cells cultured with PMNs or PMNs-conditioned medium isolated from tumour bearing and normal rats. The interaction between tumour cells and PMNs induced a decrease in ICAM-1 expression in tumour cells as well as an increase in MMP2 and tumour cell motility. Besides, conserved expression of uPAR and MT1-MMP in tumour cells was also demonstrated. The up-regulation in MMP2 associated with uPAR and MT1-MMP conserved expression may be related to an increased extracellular matrix proteolysis. These results showed that the interaction of tumour cells with PMNs could favour tumour cell spreading through the promotion of a tumour invasive phenotype.     

Mesenteric solitary fibrous tumour containing metastasis from breast carcinoma: an unusual example of tumour to tumour metastasis

Tumour to tumour metastasis is a relatively rare but well documented phenomenon. The most frequent donor tumour is lung carcinoma, and renal cell carcinoma is by far the most common recipient. Here we present a case of a 46-year-old man operated for a mesenteric tumour, which showed histological and immunohistochemical features of a solitary fibrous tumour. However, on section contained a 3.5 mm focus of an epithelial component. After a search in the past medical records it was known that the patient had been operated 3 years earlier for breast carcinoma. The epithelial component in the present tumour showed similar histological and immunohistochemical features. This is the first example of a tumour to tumour metastasis where breast carcinoma has metastasized to mesenteric solitary fibrous tumour.     

Morphological characteristics of tumours formed by Lewis lung carcinoma-derived cloned cell lines with different metastatic potentials: structural differences in their basement membranes formed in vivo

Summary Tumour basement membrane (BM) is an extracellular matrix produced by tumour cells of epithelial origin. We examined the structure and function of the tumour BM of tumour tissues formed by Lewis lung carcinoma-derived cloned cell lines (P29, LM12-3 and LM60-D6 cells) with low, medium and high metastatic potentials, respectively. Immunohistochemical staining of major BM constituents laminin and type IV collagen demonstrated that all the cell lines produced and deposited these materials extracellularly in vivo. However, the continuity of the tumour BM composed of these materials was much greater in the higher metastatic LM12-3 and LM60-D6 tumours than in those with the low metastatic P29 tumour. Electron microscopic examination revealed that in the higher metastatic tumours, especially the LM60-D6 tumour, the tumour BM had a highly organized structure consisting of lamina densa and lamina rara. Parallel bilayers of BM and their fusion were often observed and tumour cells were in direct contact with the BM. In the vicinity of tumour blood vessels, similar interactions between the tumour bM and the vascular BM were observed, and the tumour cells rested on their own BM, the fused BM or the vascular BM. In contrast, in the low metastatic tumour in which the tumour BM was not clearly defined, this close contact between tumour cells and the vascular BM was not observed. In vitro studies showed that the higher metastatic cells adhered more firmly than the LMP cells to a subendothelial matrix. These results suggest that the adhesiveness of tumour cells to the vascular BM in vivo is correlated with their ability to form an integrated BM in vivo, and that this adhesiveness of the tumour cells may be mediated in part by the tumour BM via BM fusion.     

Tumour angiogenesis: vascular growth and survival

Angiogenesis starts at the edge of a malignant epithelial tumour concurrently with tumour cell invasion and stromatogenesis, i.e. the formation of specific connective tissue stroma amenable to easy penetration by endothelial and tumour cells. However, as the tumour continues its growth, the edge becomes the inner tumour area, and a new invading tumour front is formed by the multiplying malignant cells which outflank the initial edge. This process, which repeats itself again and again, forms the "relay race" model of tumour vascular growth and regression. At the heart of the tumour unfavourable environmental conditions prevail -- hypoxia, acidity, lack of nutrients, failure of waste removal, and apoptosis rather than proliferation. Blood vessels and tumour cells are greatly decreased, but do not vanish, as tumour cells are shifting to anaerobic glycolysis, and blood vessels are turning into anti-apoptotic pathways -- vascular survival ability (VSA). Thus, assessing vascular density (VD) by simply counting "hot spots" at the edge of a tumour, where conditions are most favourable, is futile; it may reflect tumour angiogenic activity (TAA), but is not representative of genuine tumour vasculature. By combining vessel counts at the invading tumour front with those of the inner tumour areas a complete picture of tumour VD can be achieved. The thus formed four patterns of vascularization, designated as "edvin" (edge vsinner tumour area), are: edvin 1: low TAA/low VSA; edvin 4: high TAA/high VSA; edvin 2: low TAA/high VSA; and edvin 3: high TAA/low VSA. It is expected that this scheme will prove useful in the field of chemoradiotherapy and anti-angiogenic treatment.     

Tumour vascularity and proliferation: clear evidence of a close relationship.

Evaluation of various prognostic factors often reveals that some are closely related. In this issue of the Journal of Pathology, evidence is presented linking intratumoural microvessel density with tumour cell proliferation. This is expected, because an adequate blood vascular system is necessary for effective tumour cell proliferation. The blood vascular supply of a tumour is critical not only in providing tumour cells with nutrients, oxygen, and waste elimination, but also because activated endothelial cells release important paracrine growth factors for tumour cells and secrete collagenases, urokinases, and plasminogen activator. The latter allow capillary ingrowth and the spread of tumour cells into and through the adjacent fibrin-gel matrix, connective tissue stroma, and into the lymphatic and/or vascular spaces. Finally, an adequate vascular supply helps to 'switch off' apoptosis and prevent other forms of tumour necrosis, thus contributing to overall tumour growth and spread.     

Prognostic criteria in renal cell cancer

Survival of 94 patients with hypernephroma is evaluated kinetically. The following factors were analysed: sex, age, tumour size, tumour invasion in the fibrous renal capsule, venous invasion, morphologic variant of the tumour, differentiation degree, angiographic tumour type. The main factors affecting the prognosis appeared to be tumour invasion in the fibrous renal capsule and the degree of tumour differentiation. Adenocarcinoma has a better prognosis.     

A testosterone-producing tumour in the mesovarium

An androgen-secreting adnexal tumour is presented. The tumour was a steroid cell tumour of the mesovarium, without crystals of Reinke, hence the diagnosis was a steroid cell tumour (lipid cell tumour), not otherwise specified (in this case, because of its location in the mesovarium, an adrenal rest tumour). The clinical presentation, diagnosis, prognosis and differential diagnosis of virilizing adnexal tumours are discussed.     

Sinonasal haemangiopericytoma‐like tumour: a sinonasal glomus tumour or a haemangiopericytoma?

AIMS: Sinonasal haemangiopericytoma-like tumour is controversial with regard to its nosologic nature. This study aims to investigate its relationship with glomus tumour and haemangiopericytoma. METHODS AND RESULTS: Six cases of sinonasal haemangiopericytoma-like tumours identified in our files were reviewed for clinicopathological features, and compared with five cases each of soft tissue glomus tumour and meningeal haemangiopericytoma. Immunohistochemical studies for muscle-specific actin, smooth muscle actin, desmin and CD34 were performed. Sinonasal haemangiopericytoma-like tumour demonstrated a uniform histological appearance with bland-looking short, spindly cells forming sheets and short fascicles. The tumour cells were interspersed with slit-like, round and ectatic blood vessels. Actin immunoreactivity was demonstrated in all six cases, although occasionally patchy. The histological appearance and immunohistochemical phenotype of sinonasal haemangiopericytoma-like tumour were very similar to and focally indistinguishable from glomus tumour. Meningeal haemangiopericytoma, in contrast, was characterized by high tumour cellularity, random nuclear orientation, presence of staghorn vasculature and lack of immunohistochemical evidence of myogenic differentiation. CONCLUSIONS: We conclude that sinonasal haemangiopericytoma-like tumour is biologically close to or identical to glomus tumour, but is not related to haemangiopericytoma.     

Primitive small round cell tumour of the adrenal gland presenting with fever of unknown origin and t(12;22)(q13;q12) cytogenetic finding

This report describes a left adrenal tumour in a 16 year old Chinese girl who presented with fever of unknown origin. The histological and ultrastructural features of the adrenal tumour were those of a primitive small round cell tumour with neuroendocrine differentiation. Cytogenetic analysis of cultured tumour cells showed a reciprocal translocation t(12;22)(q13;q12). This is the first example of such a tumour being reported in the adrenal gland. The adrenal tumour was also the cause of the fever, which subsided after the removal of the tumour.     

Effects of high and low dietary fat and indomethacin on tumour growth, hormone receptor status and growth factor expression in DMBA-induced rat breast cancer.

The effects of high and low dietary fat (20% vs. 0.5% corn oil), and of the prostaglandin synthetase inhibitor indomethacin (0.005% w/w), on tumour incidence, tumour growth, hormone-receptor status and growth-factor expression were examined in dimethylbenzanthracene (DMBA)-induced rat breast cancer. The high dietary-fat group showed a significantly higher tumour incidence, larger tumour size and larger number of bromodeoxyuridine(BrdU)-positive cells of tumours as compared with those in the low dietary-fat group. Indomethacin reduced tumour incidence significantly, but conversely increased the tumour size and the number of BrdU-positive cells in both the high and the low dietary-fat groups. No significant difference was noted in the hormone-receptor status of the tumours. Growth factors (TGF-alpha and IGF-II) were somewhat highly expressed in the high dietary-fat group as compared with the low dietary-fat group, but indomethacin rather reduced the growth-factor expression. It is concluded that high dietary fat stimulates tumour incidence and tumour proliferation, while indomethacin has dual effects: a stimulating effect on tumour proliferation, but an inhibiting effect on tumour incidence. It is also suggested that hormone-receptor status and growth-factor expression do not play an important role in their stimulating effects on tumour proliferation.     

Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients

Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than 1 cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung tumours. However, to make SMART an efficient technique in general, it is found that breath coaching techniques are required.     

Adhesion molecule expression in breast cancer: the phoenix in tumour metastasis?

Adhesion molecules have a number of diverse roles, amongst which is the control of tissue architecture and the maintenance of tissue integrity. Most tumours have an abnormal architecture and loss of tissue integrity is thought to be an important step in the development of local invasion. Thus, alterations in adhesion molecules may have a role in both tumour development and tumour invasion. The role of these molecules in the establishment of tumour metastases is much less certain. The tumour cells in a metastatic deposit are in a different environment and are faced with a different set of selection pressures, which may drive tumour evolution in a new direction. Metastatic deposits often resemble the tumour of origin and not infrequently show better differentiation. Together with evidence from experimental maintenance systems which shows that maintenance of intercellular contact may prevent apoptosis, this implies a role for adhesion molecules in tumour metastasis.     

The retroperitoneal surface in distal caecal and proximal ascending colon carcinoma: the Cinderella surgical margin?

BACKGROUND: Mesorectal margin tumour involvement is a predictor of local recurrence in rectal carcinoma and an indication for postoperative radiotherapy in suitable patients. However, the prevalence of non-peritonealised surgical margin involvement in ascending colon carcinoma is unknown. AIMS: To test the hypothesis that retroperitoneal surgical margin (RSM) tumour involvement occurs in distal caecal and proximal ascending colon carcinoma. METHODS/RESULTS: One hundred right hemicolectomy specimens, removed for adenocarcinoma of the caecum or proximal ascending colon, were studied. During routine specimen dissection, at least one additional tissue block was taken to include the tumour and the RSM. The tumour distance from the RSM was recorded. RSM tumour involvement was present in seven cases (7%). Direct (non-nodal) RSM tumour involvement (five cases) only occurred in posterior or circumferential tumours. CONCLUSIONS: RSM tumour involvement occurs within a considerable number of distal caecal and proximal ascending colon carcinomas. The rate of RSM tumour involvement identified here is similar to a previously published local recurrence rate of 10% in caecal carcinoma, suggesting that RSM tumour involvement may be a predictor of recurrence in these tumours. Therefore, patients with distal caecal or proximal ascending colon carcinoma and RSM tumour involvement may benefit from postoperative radiotherapy.     

Carcinoid tumour metastatic to the orbit with infiltration to the extraocular orbital muscle

Ninety-three percent of symptomatic patients with small intestinal carcinoid tumours have metastases. The most common sites of metastases are lymph nodes and liver. Orbital metastases have rarely been described and the majority of them involve the choroid rather than extraocular orbital structures. We report a patient who developed proptosis, impairment of vision and reduced ocular motility on the left side, eighteen months after operation for primary intestinal carcinoid tumour with hepatic metastases. CT and MR studies revealed the tumour mass infiltrating the inferior rectus muscle. Biopsy examined by imprint and frozen section showed tumour consistent with metastatic carcinoid. The tumour was removed. HE and staining for cytokeratin, chromogranin, NSE, serotonin, somatostatin and gastrin showed that the tumour tissue corresponded to that of the primary intestinal carcinoid tumour. Intramuscular orbital metastasis from a carcinoid tumour is a rare occurrence. Diagnosis may be difficult, especially where no evidence of primary carcinoid tumour is present. Metastatic orbital carcinoid should be suspected in patients with a clinical history of carcinoid tumour and who develop ocular complaints and mass lesion in the orbit. Complete surgical removal of the tumour is important for optimal restitution of vision and eye movements.     

The tumour–stroma ratio in colon cancer: the biological role and its prognostic impact

The tumour microenvironment consists of a complex mixture of non‐neoplastic cells, including fibroblasts, immune cells and endothelial cells embedded in the proteins of the extracellular matrix. The tumour microenvironment plays an active role in tumour behaviour. By interacting with cancer cells, it influences disease progression and the metastatic capacity of the tumour. Tumours with a high amount of stroma correspond to poor patient prognosis. The tumour–stroma ratio (TSR) is a strong independent prognostic tool in colon cancer and provides additional value to the current clinically used tumour–node–metastasis classification. The TSR is assessed on conventional haematoxylin and eosin‐stained paraffin sections at the invasive front of the tumour. Here we review studies demonstrating the prognostic significance of the TSR in solid epithelial tumours with a focus on colon cancer. Moreover, the biological role of the tumour microenvironment during tumour progression and invasion will be discussed, as well as the attempts to target the tumour stroma for therapeutic purposes. We suggest that the TSR can be implemented with little effort and without additional costs in current routine pathology diagnostics owing to its simplicity and reliability.     

Plexiform angiomyxoid myofibroblastic tumour: differential diagnosis of gastrointestinal stromal tumour in the stomach

Mesenchymal tumours other than gastrointestinal stromal tumours are rare in the stomach. Nevertheless it is important to incorporate them into the differential diagnosis. Plexiform angiomyxoid myofibroblastic tumour is a recently described new entity of a presumably benign mesenchymal gastric tumour. This report presents what is believed to be the third case of this tumour. The tumour is characterised by bland spindle cells in a plexiform pattern, a mucinous extracellular matrix and a network of thin blood vessels. These findings are completely in line with the two previous reported cases. There was a strong positivity for alpha-smooth muscle actin and a low proliferation index (<2%). The tumour had no C-KIT or CD34 expression and no mutation in the C-KIT and PDFGRalpha genes. Plexiform angiomyxoid myofibroblastic tumour may present a new mesenchymal tumour entity in the stomach.     

Brenner tumour of the vagina

Vaginal tumours are rare, and Brenner tumour is one of the most infrequent vaginal lesions. Brenner tumour is a transitional tumour that typically arises in the ovaries. Some cases have been reported in the broad ligament, uterus and paratesticular structures. Only five cases have been reported in the vagina. We report a sixth case and discuss the histogenesis of this tumour, as well as the differential diagnosis with the mixed tumour of the vagina.