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Ultrasonographic differentiation of hepatocellular carcinoma from metastatic liver cancer.

Ultrasonographic features of tumor nodules in 64 patients with hepatocellular carcinoma and 87 with metastatic liver cancer were analyzed for differential diagnosis. Sonographic characteristics of hepatocellular carcinoma were the mosaic, posterior echo enhancement, and lateral shadow patterns, which were rarely observed in metastatic liver cancers. Small hepatocellular carcinomas, less than 3 cm in diameter, showed a hypoechoic pattern. Metastatic liver cancers originating from the gastrointestinal tract were frequently hyperechoic irrespective of their size and the bull's-eye-like pattern was specific for metastases from the lung. These results indicate that ultrasonography is useful for the differential diagnosis of hepatocellular carcinoma and metastatic liver cancer.

Carcinoma, Hepatocellular↗

Invasive micropapillary carcinoma of the breast.

Nine examples of a rare variant of invasive breast carcinoma characterized by the formation of micropapillae within clear spaces separated by a fibrocollagenous or delicate fibrovascular stroma are presented. Designated as invasive micropapillary carcinoma, the unusual morphology of this tumor requires its distinction from metastatic ovarian serous papillary carcinoma and extensive vascular/lymphatic invasion by either a primary or metastatic breast carcinoma. The micropapillary pattern is retained in metastatic foci and areas of recurrence. This pattern also occurs admixed with regular infiltrating duct carcinoma either in the primary mammary tumor or when it recurs.

Adult↗

Time-varying hazard rates reveal patterns of progression in HR+/HER2- metastatic breast cancer: Towards risk-adapted monitoring.

BACKGROUND: optimal imaging intervals for patients with hormone receptor-positive/HER2-negative metastatic breast cancer (MBC) remains undefined. Aim of this study was to analyze the temporal patterns of disease progression to identify high risk subgroups that may benefit from intensified monitoring. METHODS: we analyzed 149 hormone receptor-positive/HER2-negative MBC patients prospectively enrolled in the MAGNETIC.1 trial (NCT05814224) and treated with first line endocrine therapy. Hazard rates (HR) for disease progression were determined according to clinico-pathological and liquid biopsy features. RESULTS: in the overall population, two distinct progression-risk peaks emerged at 2-3 months (32.9/1000 person-months) and at 24 months (28.0/1000). Higher risk of progression was observed in lobular carcinoma (61.1) [HR 61.12 per 1000 person month (pm)], progesterone receptor-negative status (HR 39.07), fulvestrant-based treatment (HR 46.88), liver metastases (HR 59.00), and presence of ≥ 3 metastatic sites (HR 40.10). CONCLUSIONS: Hazard distribution in hormone receptor-positive/HER2-negative MBC is biphasic and modulated by readily available clinical variables. High-risk subgroups may benefit from intensified radiologic and liquid-biopsy surveillance during the first three months and around two years after treatment start.

Breast cancer↗

Expression of PNA-binding sites on specific glycoproteins by human melanoma cells is associated with a high metastatic potential.

Lectin-binding patterns of seven human melanoma clones and variants selected from the same parental cell line and differing in their spontaneous metastatic potential in an animal model were compared by flow cytometry and Scatchard analysis. Human melanoma clones and variants with high and low metastatic potential could be distinguished by their peanut agglutinin (PNA)-binding patterns, but not by their wheat germ agglutinin (WGA)-, Ulex europaeus agglutinin I (UEA I)-, and soybean agglutinin (SBA)-binding patterns. Low metastatic clones and variants proved to be made up of single poorly peanut agglutinin-binding cell population (2.20-3.52 x 10(6) sites/cell, Ka = 2.48-2.75 x 10(6) M-1). By contrast, highly metastatic variants were found to be constituted by two cellular subpopulations, exhibiting respectively a moderate 2.62-3.72 x 10(6) sites/cell) and a high peanut agglutinin staining (17.68-18.76 x 10(6) sites/cell). One highly metastatic clone was found to be homogeneously constituted by a single population of cells strongly binding this lectin (18.86 x 10(6) sites/cell) with an association constant of 4.06 +/- 10(6) M-1. Using an EPICS V cytometer, these two subpopulations were sorted from a highly metastatic variant and tested for their metastatic abilities: cells with high PNA binding generated a higher frequency of metastases than did moderately PNA-binding cells. Following treatment with Vibrio cholerae neuraminidase, all cells from all variants and clones were brightly labeled by PNA, collecting in a single peak with similar fluorescence intensities. Electrophoresis of total cellular proteins and subsequent detection with labeled PNA om Western blots show two major PNA-reactive glycoproteins with apparent molecular weights of 140 and 110 kDa (MAGP1 and MAGP2), expressed only in highly metastatic cells, but which can be strongly labeled by PNA in slightly metastatic cells following a treatment with neuraminidase. These results provide evidence that the expression of terminal galactose (beta 1-3)N-acetyl galactosamine structure, positioned on MAGP1 and MAGP2 glycoproteins, is associated with the metastatic potential of human melanoma cells.

Arachis↗

Gene expression patterns and profile changes pre- and post-erlotinib treatment in patients with metastatic breast cancer.

PURPOSE: To delineate gene expression patterns and profile changes in metastatic tumor biopsies at baseline and 1 month after treatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib in patients with metastatic breast cancer. EXPERIMENTAL DESIGN: Patients were treated with 150 mg of oral erlotinib daily. Gene expression profiles were measured with Affymetrix U133A GeneChip and immunohistochemistry was used to validate microarray findings. RESULTS: Estrogen receptor (ER) status by immunohistochemistry is nearly coincided with the two major expression clusters determined by expression of genes using unsupervised hierarchical clustering analysis. One of 10 patients had an EGFR-positive tumor detected by both microarray and immunohistochemistry. In this tumor, tissue inhibitor of metalloproteinases-3 and collagen type 1 alpha 2, which are the EGF-down-regulated growth repressors, were significantly increased by erlotinib. Gene changes in EGFR-negative tumors are those of G-protein-linked and cell surface receptor-linked signaling. Gene ontology comparison analysis pretreatment and posttreatment in EGFR-negative tumors revealed biological process categories that have more genes differentially expressed than expected by chance. Among 495 gene ontology categories, the significant differed gene ontology groups include G-protein-coupled receptor protein signaling (34 genes, P = 0.002) and cell surface receptor-linked signal transduction (74 genes, P = 0.007). CONCLUSIONS: ER status reflects the major difference in gene expression pattern in metastatic breast cancer. Erlotinib had effects on genes of EGFR signaling pathway in the EGFR-positive tumor and on gene ontology biological process categories or genes that have function in signal transduction in EGFR-negative tumors.

Biomarkers, Tumor↗

Pseudogliomatous growth pattern of anaplastic small cell carcinomas metastatic to the brain.

Carcinomas metastatic to the brain usually grow very well circumscribed, with sharp delineation. Radiosurgery takes advantage of this fact by using the gamma knife for definitive treatment of small metastases. We report a systematic study of the growth pattern of cerebral metastases, focusing on tumor delineation. In 26 cases of 66 metastatic anaplastic small cell carcinomas and in one case of adenocarcinoma, we observed poorly defined borders and a highly diffuse pattern of invasion. Infiltrating carcinoma cells changed to an elongated shape adapting to preexisting tissue structures. This pseudogliomatous growth pattern of some brain metastases--apparently most likely in neuroendocrine carcinomas--is of potential importance for therapeutic strategies in the treatment of brain metastases, especially when considering treatment with radiosurgery and gamma knife.

Biomarkers, Tumor↗

Malignant melanoma metastatic to a basal cell carcinoma simulating the pattern of a basomelanocytic tumor.

We report a case of metastatic melanoma colliding with and colonizing a basal cell carcinoma (BCC) on the head of a 69-year-old man. The man had a prior history of multiple primary BCCs and melanomas. One of his primary melanomas, on the left scalp, recurred locally and resulted in the development of numerous in-transit metastases. A bluish nodule was noted on the postauricular area with clinical features consistent with a pigmented BCC. Dermoscopy showed some large gray-blue ovoid structures and blood vessels, features also consistent with BCC. However, the histologic features revealed that the nodule consisted of both metastatic melanoma as well as BCC. Melanoma was present adjacent to as well as within the epithelium of the BCC. The intimate association of melanoma cells within the nodules of BCC simulated the pattern of so-called "malignant basomelanocytic tumor," a recently proposed novel entity. To our knowledge, this is the first description of metastatic melanoma colonizing a BCC.

Aged↗

Disease patterns and survival rate in children with metastatic soft-tissue sarcoma. A report from the Intergroup Rhabdomyosarcoma Study (IRS)-I.

The patterns of disease extent, response to treatment, and survival rates were examined in 129 children registered as metastatic (Group IV) soft-tissue sarcoma patients on the Intergroup Rhabdomyosarcoma Study (IRS)-I protocol from November 1972 through October 1978. The patients' ages at diagnosis ranged from 3 months to 21 years (median, 10.5 years); 72 were male patients and 57 were female patients (male-to-female ratio, 1.3:1). The tumor arose in an extremity in 34 patients, the head and neck (exclusive of the orbit) in 27, the genitourinary tract in 25, the retroperitoneum or pelvis in 14, the trunk in 12, the intrathoracic region in nine, the hepatobiliary system in four, the perineum in two, and the orbit in two patients. The histologic types of soft-tissue sarcoma confirmed by the pathology review committee were embryonal rhabdomyosarcoma in 68 patients, alveolar rhabdomyosarcoma in 41, undifferentiated sarcoma in 14, embryonal-botryoid in two, pleomorphic in one patient, and other sarcoma in three patients. Of 105 patients who were confirmed in Group IV and had complete information concerning sites of metastatic deposits, 53 patients presented with metastases restricted to only one anatomic region or tissue; the other 52 had diffuse metastases. The most common sites of distant tumor deposits were the lungs, bone marrow, and other soft tissues. After treatment with vincristine, dactinomycin, and cyclophosphamide with or without Adriamycin (Adria Laboratories, Inc., Columbus, OH) and radiation therapy, 65 (50%) of the 129 eligible patients achieved complete disappearance of all detectable tumor. The likelihood of achieving and maintaining a complete response for 2 years was highest among patients whose tumors originated in the genitourinary tract, retroperitoneum-pelvis, or the hepatobiliary or perineum regions. Thirteen of these 45 children (29%) are alive and disease-free at a minimum of 2 years after initiation of treatment. Only 10 of the other 84 (8%) are surviving disease-free at 2 years (P = 0.02). The presence of restricted rather than diffuse metastases at diagnosis (P = 0.02) was the only other characteristic significantly related to long-term complete remissions. One hundred and two patients (79%) died at a median of 47 weeks after diagnosis, 92 from sarcoma and ten from other causes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Chemotherapy in metastatic gastric cancer: population-based perceptions and practice patterns of medical oncologists.

Although randomised trials in metastatic gastric cancer have shown a survival benefit from chemotherapy, a significant proportion of medical oncologists do not believe that it prolongs survival or improves quality of life, including those who routinely treat metastatic gastric cancer. There was wide variation in what was considered to be 'standard therapy' and a statistically significant difference between what medical oncologists consider 'standard therapy' and what they use in every day practice.

Antineoplastic Combined Chemotherapy Protocols↗

Poorly differentiated insular thyroid carcinoma. A case report with identification of intact insulae with fine needle aspiration biopsy.

BACKGROUND: Subsequent to the publication of a report in 1984 entitled "Poorly Differentiated ("Insular") Carcinoma: A Reinterpretation of Langhans "wuchernde Struma," poorly differentiated insular thyroid carcinoma (PDITC) has become recognized as a distinct thyroid neoplasm. It is classified morphologically and biologically as an intermediate entity between well-differentiated (papillary and follicular) and undifferentiated (anaplastic) thyroid carcinomas. Only a few publications have addressed the findings with fine needle aspiration biopsy (FNAB). CASE: A 67-year-old female presented for evaluation of a massively enlarged thyroid gland. Fine needle aspiration biopsy of the thyroid with a 22-gauge needle showed many large, multilayered, round to oval nests of tumor cells, 0.2-0.4 mm in diameter. Rosettelike configurations of 8-15 cells, 0.025-0.050 mm in diameter, were also observed. Nests of neoplastic cells in the histologic sections were virtually identical to those in the fine needle aspiration biopsy specimens. When the patient developed metastatic cervical adenopathy one year later, a microfollicular pattern was seen on both the FNAB and histologic sections. CONCLUSION: When nests of tumor cells, 0.2-0.4 mm in diameter, are identified in a thyroid FNAB specimen, PDITC should be included in the differential diagnosis. A microfollicular pattern in a metastatic lymph node does not exclude the possibility that the primary tumor is a PDITC.

Aged↗

Mammographic appearance of axillary lymph node calcification in patients with metastatic ovarian carcinoma.

OBJECTIVE: We describe the mammographic appearance of axillary lymph node calcification in three patients with metastatic ovarian carcinoma. CONCLUSION: Axillary lymph node calcification may be identified mammographically in patients with metastatic ovarian carcinoma and may be evidence of unsuspected metastatic disease. The pattern of calcification differs from that seen with metastatic breast carcinoma.

Aged↗

Preoperative esophageal cancer staging: magnetic resonance imaging of lymph node with ferumoxtran-10, an ultrasmall superparamagnetic iron oxide.

BACKGROUND: Accurate detection of metastasis to lymph nodes is an essential component of the approach to treatment. The purpose of this study was to evaluate the utility of magnetic resonance imaging with ferumoxtran-10 in diagnosing lymph node metastasis in esophageal cancer. STUDY DESIGN: Sixteen patients with esophageal cancer who were scheduled for surgical lymph node dissection were enrolled. All patients underwent MRI scanning before and 24 hours after intravenous administration of ferumoxtran-10, an ultrasmall, superparamagnetic iron oxide. The presence or absence of metastasis was identified in lymph nodes by their enhancement patterns. Nonmalignant nodes contained macrophages that phagocytosed ferumoxtran-10. Metastatic nodes exhibited a decrease in phagocytic activity, and consequently showed little or no uptake of ferumoxtran-10. So we subdivided the enhancement patterns into the following three patterns: (A) node having an overall low signal intensity, (B) node having an area of high signal intensity, and (C) node having an overall high signal intensity. We identified that patterns (B) and (C) were metastatic patterns. The imaging results were compared with histopathologic findings. RESULTS: Of the 408 resected lymph nodes, imaging results of 133 nodes could be compared with histopathologic findings. Twenty-four lymph nodes had histopathologic metastases. Using our enhancement criteria, sensitivity was 100%, specificity was 95.4%, and accuracy was 96.2% for diagnosis of metastatic nodes. CONCLUSIONS: Ferumoxtran-10 is useful for characterizing benign or malignant lymph nodes in esophageal cancer patients based on the defined enhancement criteria.

Adult↗

Brain metastases. Histology, multiplicity, surgery, and survival.

BACKGROUND: With the advent of new therapies for metastatic carcinoma to the brain, patterns of intracranial disease and factors influencing survival become important considerations when examining potential treatment options. METHODS: The records of 729 patients with metastases to the brain treated during the period between 1973 to 1993 were reviewed. RESULTS: Primary tumor histologic type in order of descending frequency included nonsmall cell lung carcinoma (NSCLC), breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown primary carcinoma. There were 384 patients (53%) with a single brain metastasis, which was encountered most commonly in patients with prostate carcinoma and least often in patients with SCLC. Multiple metastases were present in 345 patients (47%). The median duration from diagnosis to presentation with a brain metastasis was 12 months, ranging from 3 months for patients with NSCLC to 53 months for patients with breast carcinoma. The median duration from presentation with brain metastases to death was 4 months, ranging from 3 months for patients with SCLC to 13 months for patients with prostate carcinoma. Median survival from presentation with brain metastases to death was 5 months for patients with single lesions and 3 months for patients with multifocal disease (P = 0.0001). Median survival for patients with a single lesion was 11 months with surgery and 3 months without surgery (P = 0.0001). Surgery did not significantly influence survival in patients with multiple metastases. CONCLUSIONS: Dissemination of systemic carcinoma to the brain continues to carry a poor prognosis. Knowledge of the metastatic patterns and limited survival associated with specific tumor types may be useful for guiding future therapeutic intervention.

Brain Neoplasms↗

Nuclear DNA content and chromatin pattern of rat rhabdomyosarcoma cell sublines with different metastatic potentials.

There is a constant need of features able to characterize potentially metastatic cells among the heterogeneous cell subpopulations which constitute a tumor. Image cytometry of metastatic tumor cells give rise to variable results, partly because of a heterogeneous origin of cells, or potential drug effects. The aim of this work was to characterize nuclear changes observed in metastatic cell clones issued in vitro from the same parental cell population The nuclear phenotypes of 6 cell sublines isolated from a rat rhabdomyosarcoma cell line and differing in their metastatic ability were evaluated by image cytometry on Feulgen-stained preparations. Densitometric [5], geometric [3] and textural [9] features were computed from each nuclear image. For each cell subline, a metastatic score, ranging from 0 to 10, was calculated on the basis of in vivo invasivity data, by measuring the number of pulmonary metastases observed after s.c. graft of tumor cells in rats. Data obtained were compared to karyotype, growth characteristics, and oncogene expressions of cell lines. The nuclear DNA content, the chromosome numbers, the cell sublines doubling times, and the distribution of cells within the cell cycle appear unrelated with this score. On the contrary, increase in metastatic ability is accompanied by changes in chromatin pattern as assessed by textural features. Progressive increase in chromatin condensation can be observed in cell sublines with increasing metastatic score. These results were confirmed by an unsupervised multivariate partitioning of rhabdomyosarcoma cells which identified two separate subsets whose distributions within the analyzed cell lines correlate with their metastatic ability. These data suggest that, in rat rhabdomyosarcoma cell sublines, metastatic ability could be associated with nuclear morphological changes at the level of chromatin texture.

Animals↗

Real-world estrogen receptor alpha 1 (ESR1) testing patterns and results for ER+/HER2- metastatic breast cancer in the United States, 2018-2024.

PURPOSE: To understand historical and recent ESR1 testing rates, and when ESR1 mutations emerge during first-line (1 L) treatment. METHODS: This retrospective, observational cohort study used the Flatiron Health Research Database (FHRD) and the Flatiron Health-Foundation Medicine metastatic breast cancer (mBC) Clinico-Genomic Database (CGDB). Adult patients with a confirmed diagnosis of hormone receptor-positive/human epidermal growth factor receptor 2-negative mBC from 1/1/2018 to 6/30/2024 were included. ESR1 testing patterns and test results were descriptively analyzed. RESULTS: Among 7772 patients with mBC in the FHRD who initiated 1 L therapy, tumor ESR1 mutation status was evaluated for 222 (3%) patients at baseline (≤ 90 days before 1 L) and 1355 (17%) during 1 L. The percentage of patients who had an ESR1 test result reported during 1 L increased over time (11% in 2018-19, 19% in 2020-21, 22% in 2022-24). Median time from 1 L start to first ESR1 test was 7.4 months (mos) among tested patients. A positive test result was reported for 29/222 (13%) patients tested at baseline and 240/1355 (18%) tested during 1 L. Most (60%) tests during 1 L used tissue specimens, while the remaining 40% were liquid biopsies, and the median time from specimen collection to result reporting in 1 L was 28 (IQR:10-84) days. Focusing on time periods wherein specimens were provided, ESR1 test positivity was 6.7% (76/1,127) for specimens provided at baseline, 23% (15/65) for specimens provided 9 to 12 months into 1L therapy, 38% (26/69) for those provided 15 to 18 months into 1L, and 40% (38/94) for those provided from 18 to 24 months into 1L. CONCLUSIONS: ESR1 mutations can be detected at any time interval during 1L. CLINICAL TRIAL NUMBER: Not applicable.

Adult↗

Splenic metastasis in hairy cell leukemia.

BACKGROUND: Splenic metastasis is uncommon and usually occurs in the setting of widespread visceral metastasis. Splenic metastasis as an initial manifestation of disease and sole site of metastasis has not been reported previously. METHODS: The authors describe a patient with hairy cell leukemia (HCL) with the unexpected finding of metastatic adenocarcinoma in the spleen. Direct inspection at the time of laparotomy and subsequent radiographic studies did not show a primary or additional metastatic tumor. Eventually, he manifested evidence of pulmonary and hepatic metastases and died with fungal sepsis. RESULTS: The splenectomy specimen showed HCL and metastatic adenocarcinoma. Immunohistochemical studies showed adenocarcinoma with diffuse cytoplasmic staining for prostate-specific antigen and focally positive results with prostatic acid phosphatase antigen. Postmortem examination 9 months later showed HCL and widespread metastatic adenocarcinoma. No primary tumor was identified, and multiple tissue blocks of the prostate had negative findings for tumor. CONCLUSIONS: The immunohistologic features of the metastatic adenocarcinoma were interpreted as prostatic in origin. The pattern of isolated metastatic disease in the absence of primary tumor appears to represent another possible atypical disease presentation of prostatic cancer. Hairy cell-induced structural and immunologic alterations within the splenic microenvironment may have contributed to this unique clinical presentation.

Adenocarcinoma↗

Pulmonary manifestations of extrathoracic malignant lesions.

Two of the most common thoracic manifestations of extrapulmonary malignant tumors are thoracic metastatic lesions and pulmonary thromboembolism. Recognition of the broad array of patterns of pulmonary metastatic involvement is essential for optimal management of oncology patients. In addition to the "typical" pattern of multiple bilateral nodules, patients may have solitary nodules, reticulonodular infiltrates, hilar and mediastinal adenopathy, endobronchial obstruction, pleural disease, or even normal roentgenographic findings. An awareness of the association between cancer and pulmonary thromboembolism is also valuable. The mechanisms potentially responsible for the thrombotic events associated with malignant disease are discussed, and diagnostic issues are reviewed.

Humans↗

Metastatic hepatoma originating from the pons hepatis presenting extrahepatic growth--classification of different patterns covering REX's recessus.

A metastatic liver carcinoma which developed from the pons hepatis and presented as an extrahepatic mass on ultrasonography and computed tomography is reported. There have been no other reports of hepatoma documenting the extrahepatic growth developed from the pons hepatis. Herein we study the frequency of the pons hepatis and classify the form of REX's recessus. Of 125 cases that underwent upper abdominal operation, 46 cases (38%) had nothing under REX's recessus (Type I), 48 cases (37%) had a fibrous tissue under REX's recessus (Type II), and 31 cases (25%) had a pons hepatis (Type III). In Type III, some cases suggested that the pons hepatis was ready to disconnect from side to side. We conclude that Type II is a modified form of Type III, and Type I is a modified form of Type II.

Carcinoma, Hepatocellular↗