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PubMed1990

Cutaneous papillary squamous cell carcinoma. A report of two cases.

Several histologic patterns of squamous cell carcinomas (SCC) have been described, including classical, adenoid, verrucous, and clear cell. We report 2 cases of an unusual purely exophytic papillary growth pattern. Both tumors occurred on sun-exposed skin of elderly patients and exhibited rapid growth. The tumors were red-tan and fungating, raising the clinical differential diagnoses of pyogenic granuloma, SCC, metastatic carcinoma or amelanotic melanoma. Histologically there was a prominent papillary growth pattern with several layers of notably atypical squamous epithelium overlying a fibro-vascular core in both cases. Mitoses were frequent. The tumors lacked deep invasion, although focal invasion of the stalk was present. These tumors were histologically distinct from verrucous carcinoma, verrucous Bowen's disease, and previously described adnexal carcinomas. The lack of deep invasion and the absence of local recurrence or metastatic disease after 18 months follow-up suggest that this histologic variant is a low-grade malignancy, although study of more cases and longer follow-up will be necessary to accurately assess the biology of this papillary variant of SCC. We believe that this growth pattern has not yet been described and a pure papillary form must be included as one of the histological subtypes of cutaneous SCC.

Aged↗

PubMedDate not supplied

Selection of a highly metastatic liver-colonizing subpopulation of Lewis lung carcinoma variant H-59 using murine hepatocyte monolayers.

We have previously described two highly metastatic variants of the Lewis lung carcinoma (3LL) with distinct patterns of organ-selective metastasis. Variant M-27 metastasizes exclusively to the lung regardless of the route of inoculation, whereas variant H-59 metastasizes primarily to the liver. The objective of this work was to investigate host-tumor cell interactions which determine the metastatic preference of these tumor cell lines. An in vitro adhesion assay using isotope-labelled tumor cells was utilized to compare the ability of the two cell lines to bind to murine hepatocytes. It was found that the proportion of H-59 cells which specifically bound to hepatocytes increased progressively for up to 30 min of incubation, at which time it peaked with as many as 30-50 per cent of the cells bound to the monolayers. The binding of M-27 cells was significantly lower and ranged from 4 to 8 per cent during incubation periods of up to 90 min. Hepatocyte monolayers were subsequently used to select a subpopulation of tumor H-59 enriched for highly adherent cells. This subpopulation was found to be highly metastatic to the liver, whereas the non-adherent fraction failed to give rise to hepatic metastases in most of the animals injected. DNA analysis using flow cytometry suggested that the selection was not based on cell-cycle related properties of the tumor cells. These results suggest that in the present tumor model, hepatic metastasis is closely related to and may be dependent on tumor cell binding to hepatocytes.

Animals↗

PubMed2005

Wnt-5a gene expression in malignant human neuroblasts.

Neuroblastoma (NB), an embryonal malignancy, poses a major challenge in pediatric oncology for the treatment of disseminated forms. Here, we report the decrease of Wnt-5a gene expression in high-risk NB (HR-NB) as well as in cultured metastatic neuroblasts. Wnt-5a is a member of the Wnt signaling pathway which is mainly associated with patterning decisions in the embryonic nervous system. Moreover, Wnt-5a has been involved in metastatic melanoma progression and invasive ductal breast cancer via adhesion and migration alterations. As retinoic acid (RA) plays a major role in the neural crest induction and differentiation, we showed that RA reverses the aberrant negative regulation of Wnt-5a in metastatic neuroblasts. While beta-catenin expression remained unchanged, PKC-theta, a protein kinase C isoform, was evidenced to increase and parallel Wnt-5a level. For the first time, the involvement of Wnt-5a through the Wnt/calcium signaling is highlighted in the pathogenesis of a pediatric embryonal malignancy, NB.

Cell Differentiation↗

PubMed1999

Secretory meningioma, a rare meningioma subtype with characteristic glandular differentation: an histological and immunohistochemical study of 9 cases.

AIM: We studied the immunophenotype of 9 cases of secretory meningioma (SM), a rarely reported meningioma variant, characterized by small gland-like lumina filled with a PAS-positive, diastase-resistant substance. METHODS: Three samples of arachnoid tissue and 9 SMs were studied with a panel of monoclonal antibodies (MoAbs) against cytokeratins (Ck) 7,8, 20, vimentin, EMA, CEA and the mucin epitopes sialyl-Tn, Tn, CA19.9, CA125, against the BerEP4 and CD15; 3 colonic adenocarcinomas metastatic to the brain and a case of meningioma with metastasis from a gastric signet-ring cell carcinoma were also studied with the same panel of MoAbs for comparison. RESULTS: The 3 samples of arachnoid cap cells were positive only for EMA and vimentin in the supportive stroma. All 9 SMs resulted Ck7+, Ck8+, Ck20-, EMA+, CEA and mucin epitopes+, confirming at an immunohistochemical level the glandular differentiation. Notable exceptions were the negativity for BerEP4 and CD15 antigens. Conversely, the 3 metastatic colonic adenocarcinomas to the brain were Ck7-, Ck8+, Ck20+, CEA and mucin epitopes+, BerEP4 and CD15+; the gastric signet-ring cell carcinoma metastatic to a meningioma showed the same immunophenotype as the other metastatic adenocarcinomas with the exception of BerEP4 negativity. CONCLUSION: The different pattern of cytokeratin expression (Ck7+/Ck20- for SMs, and Ck7-/ Ck20+ for adenocarcinomas) and the negativity for BerEP4 and CD15 epitopes of SMs, could be relevant for the distinction between SMs and metastatic adenocarcinomas.

Adenocarcinoma↗

PubMed2004

Contrast-enhanced intraoperative ultrasonography in surgery for liver tumors.

IOUS is the most accurate diagnostic technique for assessing focal liver lesions, but still has some drawbacks. Contrast-enhanced ultrasound examination done intraoperatively (CE-IOUS), using second generation contrast agents (SonoVue, Bracco-Imaging, Milan, Italy), seems able to overcome those aforementioned lacking aspects of IOUS. In cirrhotic patients with hepatocellular carcinoma (HCC), CE-IOUS provides information about tumor vascularity which are useful for nodules differentiation: this should improve the surgical radicality. Furthermore, two different pattern of enhancement are also recognizable at CE-IOUS in those HCC nodules depicted preoperatively: one of them has no similarity with that observed at computed tomography (CT). In patients who undergo surgery for colorectal liver metastases, CE-IOUS seems to improve the sensitivity of IOUS to small, hypoechoic lesions, reducing the risk to down-stage the disease and enhancing the rate of treatment with curative intent. In conclusion, IOUS accuracy is improved by CE-IOUS with an impact on surgical strategy either for primary than for metastatic tumors. Furthermore, a wider experience with vascular enhancement patterns at CE-IOUS could provide new classification for liver lesions.

Carcinoma, Hepatocellular↗

PubMed2003

Primary cervical adenocarcinoma with intestinal differentiation and colonic carcinoma metastatic to cervix: an investigation using Cdx-2 and a limited immunohistochemical panel.

CONTEXT: Cdx-2 is expressed in normal colonic epithelia and in most colorectal adenocarcinomas. No data exist on Cdx-2 expression in primary cervical adenocarcinoma with colonic differentiation. OBJECTIVE: To ascertain the utility of Cdx-2 and a limited immunohistochemical panel in differentiating between primary cervical adenocarcinoma with intestinal differentiation and secondary (colonic) cervical adenocarcinoma, which call for different surgical and chemotherapeutic treatment protocols. DESIGN: We examined cervical tract adenocarcinomas in women with previously negative medical histories for neoplastic disease and in women with colonic carcinoma. An immunohistochemical panel consisting of cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, and a new marker, Cdx-2, was evaluated in all cases. The clinical data, the morphologic features, and the immunohistochemical staining patterns were compared. RESULTS: Of the tumors diagnosed as metastatic intestinal adenocarcinoma of the cervix, based on clinical data and hematoxylin-eosin-stained sections, all were Cdx-2 positive, whereas Cdx-2 was not expressed in any of our cases of primary cervical adenocarcinoma with colonic differentiation. Carcinoembryonic antigen was expressed both in primary cervical tumor and in secondary (intestinal) cervical adenocarcinoma. Cytokeratin 20 was not expressed in our cases of cervical adenocarcinoma, and it was not expressed in 7.15% of cervical metastases from intestinal carcinoma. Immunostaining with cytokeratin 7 was positive in cervical adenocarcinoma, but was negative in secondary (intestinal) cervical adenocarcinoma. CONCLUSIONS: Our immunohistochemical analysis shows that Cdx-2 has good specificity and would be a good marker to use in a limited panel of immunohistochemical markers, such as cytokeratin 7, cytokeratin 20, and carcinoembryonic antigen, to distinguish primary cervical adenocarcinoma from intestinal metastases to the cervix.

Adenocarcinoma↗

PubMed2006

Congenital renal rhabdoid tumor with placental metastases: immunohistochemistry, cytogenetic, and ultrastructural findings.

Malignant congenital tumors of fetal origin are rare lesions, the most common type being congenital neuroblastoma. Although prenatal diagnosis is possible in large tumors, occasionally the tumor will be diagnosed first by its metastatic involvement of the placenta. Placental metastases can reflect either maternal or fetal primary sites, and each has relatively specific patterns of placental involvement. We describe the clinical and pathologic features of a widely metastatic congenital renal rhabdoid tumor with its placental and autopsy findings, and include the immunohistochemical, cytogenetic, and ultrastructural features. The pathologic features of the placenta in congenital renal rhabdoid tumor with placental metastasis have not been previously described. The examination of the placenta in this case led to the initial diagnosis and obviated the need for additional diagnostic procedures.

Adult↗

PubMedDate not supplied

Cell surface glycosylation and characterization of a differentially expressed glycoprotein in metastatic and non metastatic cell lines of the rat BSp73 tumor.

The highly (ASML) and non metastatic (AS) variants of the rat tumor BSp73 were compared with respect to cell surface carbohydrate proteins. Fluorescence labelling with lectins (ConA, MPA, PNA, SBA, UEA-I, WGA) revealed a differentiated carbohydrate pattern at the cell surface of these cell lines. The highly metastatic variant was significantly more glycosylated with respect to galactosyl, mannosyl and N-acetylgalactosylamine residues; fucosyl residues were exclusively expressed in the metastatic variant. Examination of isolated plasma membrane fractions showed quantitative differences with respect to glycosylated proteins separated on polyacrylamide gels. A 30 kDa glycoprotein (GP30-ASML) dominant in the metastatic variant was further characterized. Various detergents (CHAPS, Nonidet, SDS, Triton X-100) and urea extracted it exclusively from the highly metastatic variant. GP30-ASML is a predominantly O-glycosylated single polypeptide chain with terminal N-acetylgalactosamine and galactosyl residues; its molecular weight determined by SDS-PAGE is 30 kDa and its isoelectric point is 7.8. Immunofluorescence localization experiments with monoclonal antibodies specific for GP30-ASML and polyclonal antibodies raised against GP30-ASML showed this protein at the cell surface and in the lysosomal compartment of both cell lines; exclusively in the non metastatic variant it was also found in the nuclear membrane. The function of this protein is still unknown.

Adenocarcinoma↗

PubMed1996

Expression of CD44 splice variants in squamous epithelia and squamous cell carcinomas of the head and neck.

Splice variants of the adhesion molecule CD44 have been described as essential for the lymphatic spread of rat tumour cells and are claimed to be involved in the metastatic spread of several human tumours. Immunohistochemistry has been used to analyse the expression pattern of CD44 standard (CD44s) and variant (CD44v) isoforms in normal and dysplastic squamous epithelia, as well as in primary and metastatic squamous cell carcinomas (SCCs), which spread predominantly by way of the lymphatic system. Frozen sections of squamous epithelia and of squamous cell carcinomas were stained with a panel of monoclonal antibodies recognizing epitopes of CD44s as well as of the variant exons v5, v6, v7, v7-v8, and v10. The stratum basale and stratum suprabasale of squamous epithelia stained with all antibodies; the stratum spinosum stained with anti-CD44v5, anti-CD44v6, anti-CD44v7-8 and anti-CD44v10; the lower layers of the stratum corneum stained with anti-CD44v5. This expression profile was seen in epithelia of the lip, the tongue, the gingiva, the hard palate, the floor of the mouth, the buccal mucosa, and the pharynx. The same pattern of expression was also noted in dysplastic epithelia, but expression of the variant exons v7, v8, and v10 was significantly downregulated in primary squamous cell carcinomas and was not detected at all in the majority of metastasis-derived specimens. Expression of CD44v5 and CD44v6, on the other hand, was mainly unaltered. Thus, epithelial cell layers representing different stages of differentiation express distinct sets of CD44 variant isoforms, where especially exons v8-v10 might be required for the maintenance of the structural integrity of squamous epithelium. Downregulation of these exons on tumour cells could indicate that they are irrelevant for tumour progression or may even hamper infiltration of surrounding tissue or of lymphatics.

Adult↗

PubMed1988

Use of immunohistochemical methods in the differential diagnosis between primary cerebellar haemangioblastoma and metastatic renal carcinoma.

The potential role of immunohistochemistry in making the distinction between primary cerebellar haemangioblastoma and metastatic renal carcinoma was investigated by examining the reaction pattern of 10 cerebellar haemangioblastomas (seven women, three men, aged 20-40 years) and 10 primary renal carcinomas (six men, four women, aged 49-82 years) to a panel of epithelial, glial, and neural/neuroendocrine antisera. The tumour cell membranes of the renal carcinomas stained strongly with epithelial membrane antigen (EMA); membrane staining was totally absent in the haemangioblastomas. Strong neurone specific enolase (NSE) and S100 staining were also seen in haemangioblastomas but were more variable than EMA staining in renal carcinomas. It is concluded that a panel of antisera is required to distinguish between histologically similar areas in primary haemangioblastomas and metastatic renal carcinomas, and that while complementing conventional histological techniques, new problems of interpretation result which must be taken into account.

Adult↗

PubMed1989

Lipid characteristics of RSV-transformed Balb/c 3T3 cell lines with different spontaneous metastatic potentials.

To determine whether a metastatic phenotype may be correlated with a characteristic lipid pattern, we compared the lipid composition of low metastasizing Balb/c 3T3 cells transformed by the B77 strain of Rous sarcoma virus (B77-3T3 cells) with that of a subclone isolated by growth in 0.6% agar, the B77-AA6 cells, which exhibit a high capacity for spontaneous metastasis. B77-3T3 cells revealed characteristics in their lipid composition common to other systems of transformed cells, i.e., an accumulation of ether-linked lipids, a reduction of the more complex gangliosides, an increase of oleic acid (18:1) and a decrease of arachidonic (20:4) and C22 polyunsaturated fatty acids in phospholipids. High metastatic B77-AA6 cells showed: a) an even more marked decrease of complex gangliosides; b) a more pronounced increase of 18:1 and decrease of 20:4 and 22 polyunsaturated fatty acids in certain phospholipid classes; and c) a higher percentage of alkyl-acyl subfractions in both phosphatidylcholine and phosphatidylethanolamine than B77-3T3 cells. Comparing the data for other systems of metastatic cells with those of lipid studies of spontaneously metastasizing B77-AA6 cell system leads us to conclude that the metastatic phenotype is characterized by a change in ether-linked lipids, rather than in fatty acids.

Animals↗

PubMed2006

Expression profiles of metastatic brain tumor from lung adenocarcinomas on cDNA microarray.

Distant metastasis is one of the crucial parameters determining the type of treatment and prognosis of patients. Previous studies discovered important factors involved in multiple steps of metastasis, the precise mechanisms of metastasis still remain to be clarified. To identify genes associated with this complicated biological feature of cancer, we analyzed expression profiles of 16 metastatic brain tumors derived from primary lung adenocarcinoma (ADC) using cDNA microarray representing 23,040 genes. We applied bioinformatic algorithm to compare the expression data of these 16 brain metastatic loci with those of 37 primary NSCLCs including 22 ADCs, and found that metastatic tumor cells has very different characteristics of gene expression patterns from primary ones. Two hundred and forty-four genes that showed significantly different expression levels between the two groups included plasma membrane bounding proteins, cellular antigens, and cytoskeletal proteins that might play important roles in altering cell-cell communication, attachment, and cell motility, and enhance the metastatic ability of cancer cells. Our results provide valuable information for development of predictive markers as well as novel therapeutic target molecules for metastatic brain tumor of ADC of the lung.

Adenocarcinoma↗

PubMed2003

Miliary pulmonary metastases from a clinically occult pleural mesothelioma.

Mesothelioma is a rare neoplasm of the serosal membranes. Signs and symptoms of a pleural effusion typically herald discovery of the tumor. We report a case of miliary metastatic mesothelioma involving both lungs in a 54-year-old man who presented with right-sided chest discomfort, numerous pulmonary nodules detected by computed tomography of the chest, and absent pleural effusion. Immunohistochemical and electron microscopy studies performed on wedge biopsies of parenchymal pulmonary nodules led to the diagnosis of metastatic mesothelioma. Subsequent pleural evaluation and biopsy of pleural thickening noted at a site of prior chest wall trauma identified the primary neoplasm and confirmed the diagnosis as malignant epithelioid mesothelioma. The histologic appearance of discohesive epithelioid cells in a distinctly myxoid background was the clue in this case leading to the consideration of metastatic mesothelioma and a thorough immunohistochemical evaluation of the tumor. This case shows that mesothelioma may metastasize throughout the lungs in a miliary pattern and the metastases may be clinically detected before the primary pleural tumor. Metastatic mesothelioma is a consideration for metastatic pulmonary tumors of unknown origin.

Biomarkers, Tumor↗

PubMed1995

Diffuse bone marrow uptake [123I]MIBG in neuroblastoma: an "MIBG super scan" case report.

We present the case of a 3-year-old child with neuroblastoma metastatic to the bone marrow. [123I]MIBG total body scintigraphy revealed a diffuse pattern of intense fixation throughout the skeleton. This was analogous to the "super scan" described with 99mTc-MDP bone scintigraphy when extensive metastatic or metabolic bone disease is present. Essentially, a high bone-to-soft tissue ratio was found without uptake in the liver, kidney and bladder, owing to a "steal" mechanism caused by the avid bone metastases.

3-Iodobenzylguanidine↗

PubMed2006

Post-menopausal bleeding: a rare presentation of metastatic uveal melanoma.

Uveal melanoma differs from cutaneous melanoma in many ways, including its pattern of metastasis, and exhibits latency with clinical evidence of metastasis sometimes appearing many years after primary diagnosis. Most patients develop metastasis within the liver, but some may present with metastasis to other sites. We report a case of uveal melanoma that presented with post-menopausal bleeding due to metastasis. Further investigation revealed widespread metastatic disease and the patient was not fit for chemotherapy. She died two months after presentation: autopsy revealed metastases in many sites, including the uterus, right ovarian fibroma, kidney, mesentery, liver, lung, thyroid, bone marrow and skin. The immediate cause of death was cardiac tamponade due to a malignant effusion secondary to cardiac metastasis. This case illustrates the widespread metastatic potential of uveal melanoma and highlights the potential for unusual presentation of metastatic disease from this eye tumor.

Aged, 80 and over↗

PubMedDate not supplied

HOX genes in human cancers.

Knowledge about transcription factors is crucial for understanding the molecular basis of neoplasia. Homeobox-containing genes are a family of transcription factors mostly involved in normal development. Class I human homeobox-containing genes (HOX genes) are organized in four clusters on different chromosomes. The order of the genes within each cluster is highly conserved throughout evolution suggesting that the physical organization of HOX genes may be (1) essential for their expression and (2) responsible for major biological functions. We have studied HOX gene expression in several human tissues and organs as well as in their neoplastic counterparts. We have observed (a) characteristic patterns of HOX gene expression for each normal solid organ analyzed, (b) altered HOX gene expression in kidney and colon cancer, (c) a correlation between HOX gene expression and different histological types of primary small cell lung cancer (SCLC) and (d) marked alterations of HOX gene expression among primary and metastatic SCLC variant types. Furthermore, we have shown that differential patterns of HOX gene expression correlate with the adhesion profile (VLA-2, VLA-5, VLA-6 and ICAM-1) and N-RAS mutation in clonal melanoma populations isolated from a single human melanoma metastasis. This suggests that HOX genes act as a network of transcriptional regulators involved in the process of cell to cell communication during normal morphogenesis, the alteration of which may contribute to the evolution of cancer.

Adult↗

PubMed1985

Improved detection of labile cell-surface components with zinc chloride-aprotinin: demonstration of glycoprotein differences in K-1735 metastatic melanoma variants.

Metabolic labelling of K-1735 melanoma variants with 3H-glucosamine and cell harvesting with the commonly used protease inhibitor phenylmethylsulfonylfluoride revealed a Triton-insoluble fibronection-like 230 kd component in poorly metastatic cells. This component was not evident in highly metastatic cells. Significantly improved surface labelling and detection of the 230 kd glycoprotein in the highly metastatic variant was achieved by zinc chloride-aprotinin treatment of cells prior to harvesting. This procedure also revealed an increase in a trypsin-sensitive glycoprotein of higher molecular weight in the Triton-insoluble fraction of the highly metastatic cell variant. Glycoprotein labelling in this fraction showed an electrophoretic pattern strongly resembling that reported by others for the high-molecular-weight human melanoma-associated glycoprotein complex. The differential detection of the high-molecular-weight glycoprotein species in melanoma variants with differing metastatic abilities in an animal model provides a means of studying their possible relevance to metastatic melanoma. Our data also suggest that zinc chloride-aprotinin can be used to improve the detection of labile cell-surface components.

Animals↗

PubMed1991

[Radiological diagnosis of splenic metastasis and its prevalence at autopsy].

CT and US findings of 7 cases of splenic metastases are described and the prevalence of splenic metastases at autopsy in 641 cases with malignant tumors were evaluated. Metastatic foci in spleen appeared mostly as poorly-defined low density masses on CT. Iodinated contrast material was administered in 2 cases, but no contrast enhancement was observed. US showed both hypoechoic and hyperechoic patterns. These appearances were nonspecific, but were similar to those of metastatic lesions in the liver which were often visible on CT associated with splenic metastases. At autopsy splenic metastases were found in 34 of 641 cases (5.3%). Gastric, colon, lung and ovarian cancers were most common primary tumors. However, the rate of splenic metastasis per tumor was highest in ovarian cancer (50.0%), followed by malignant melanoma (33.3%), colon cancer (16.2%) and gastric cancer (8.2%). Hepatoma which had the biggest number of autopsy cases in this series showed the lowest rate of splenic metastasis (0.8%).

Aged↗