• fluorodeoxyglucose
• hepatic metastatic carcinoma of unknown primary
• positron emission tomography/computerized tomography

• Adult
• Aged
• Aged, 80 and over
• Carcinoma/diagnostic imaging
• Case-Control Studies
• Female
• Fluorodeoxyglucose F18/administration & dosage
• Fluorodeoxyglucose F18/metabolism
• Humans
• Liver Neoplasms/pathology
• Liver Neoplasms/secondary
• Male
• Middle Aged
• Neoplasm Metastasis/diagnostic imaging
• Neoplasm Metastasis/pathology
• Neoplasms, Unknown Primary/pathology
• Positron Emission Tomography Computed Tomography/methods
• Predictive Value of Tests
• Radiopharmaceuticals/administration & dosage
• Radiopharmaceuticals/metabolism
• Retrospective Studies
• Sensitivity and Specificity

Cancer can metastasize from early lesions without detectable tumors. Despite extensive studies on metastasis in cancer cells from patients with detectable primary tumors, mechanisms for early metastatic dissemination are poorly understood. Her2 promotes breast cancer early dissemination by inhibiting p38, but the downstream pathway in this process was unknown. Using early lesion breast cancer models, we demonstrate that the effect of p38 suppression by Her2 on early dissemination is mediated by MK2 and Hsp27. The early disseminating cells in the MMTV-Her2 breast cancer model are Her2^highp-p38^lowp-MK2^lowp-Hsp27^low, which also exist in human breast carcinoma tissues. Suppression of p38 and MK2 by Her2 reduces MK2-mediated Hsp27 phosphorylation, and unphosphorylated Hsp27 binds to β-catenin and enhances its phosphorylation by Src, leading to β-catenin activation and disseminating phenotypes in early lesion breast cancer cells. Pharmacological inhibition of MK2 promotes, while inhibition of a p38 phosphatase Wip1 suppresses, early dissemination in vivo. These findings identify Her2-mediated suppression of the p38-MK2-Hsp27 pathway as a novel mechanism for cancer early dissemination, and provide a basis for new therapies targeting early metastatic dissemination in Her2⁺ breast cancer.

• NGS
• biomarker
• ctDNA
• diagnosis
• glioma
• liquid biopsy
• mass-spectrometry
• oncology
• prognosis
• urological cancers

• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Cell-Free Nucleic Acids/genetics
• Circulating Tumor DNA
• Humans
• Liquid Biopsy/methods
• Liquid Biopsy/trends
• Neoplasms/diagnosis
• Neoplasms/genetics
• Neoplastic Cells, Circulating/metabolism
• Prognosis

• Biopsy
• Bone Neoplasms/diagnosis
• Bone Neoplasms/secondary
• Diagnosis, Differential
• Fluorodeoxyglucose F18
• Humans
• Male
• Middle Aged
• Neoplasms, Unknown Primary/diagnosis
• Positron Emission Tomography Computed Tomography
• Radiopharmaceuticals
• Ribs/pathology
• Tuberculosis, Osteoarticular/diagnostic imaging
• Tuberculosis, Osteoarticular/pathology

• Gastrointestinal oncology
• Metastasis
• Squamous cell carcinoma

Carcinoma of unknown primary (CUP) of the pelvis is a challenging entity for the oncologist. The role of human papilloma virus (HPV)/p16 in carcinogenesis and prognosis is more established in the head and neck than in the pelvis. In the case of an HPV positive occult primary of the pelvis the radiation therapy target coverage is not well established.

Case#1: A 69-year-old female with a left retroperitoneal and pelvic mass was treated with chemoradiation to a dose of 45 Gy in 25 fractions to elective lymph node regions and simultaneous boost to FDG-avid lymph nodes to 55 Gy in 25 fractions. A post-treatment PET-CT showed complete response of disease now 7 months post treatment. Case#2: A 58-year-old female with a large left retroperitoneal pelvic mass was treated post-operatively with chemoradiation to 45 Gy in 25 fractions with a pelvic boost to 54 Gy. She is clinically and radiographically with no evidence of disease at 4 years. Case#3: A 47-year-old female with left sided retroperitoneal pelvic mass that declined therapy. She ultimately died of progressive disease at 1 year after diagnosis.

Cisplatin based chemoradiation is effective for treating HPV/p16 + pelvic squamous cell cancers of unknown primary as long as the mass, regional lymph nodes and high risk pelvic primary sites are adequately covered.

•

Adds 3 cases of pelvic squamous cell carcinoma of unknown primary

• Carcinoma of unknown primary
• Chemoradiation
• HPV positive
• Pelvis and retroperitoneum
• Squamous cell carcinoma
• p16 positive

Metastatic malignant tumors that originate from occult primaries are defined as “cancers of unknown origin.” We herein present the case of a 59-year-old man who presented with small bowel perforation secondary to metastatic adenocarcinoma of an unknown primary site. Imaging exhibited two pulmonary nodules, neither of which was dominant, along with mediastinal and retroperitoneal lymphadenopathy. Immunohistochemical profiling of the small bowel biopsy specimens revealed the tumor was most likely pulmonary in origin.

We report a case of a 59-year-old gentleman who had suffered from low back pain for several months. Abdominal sonogram showed multiple heteroechoic nodules in the bilateral liver and an enlarged pancreatic head. Abdominal computer tomography (CT) favored pancreas head tumor with liver and bone metastasis. Endoscopic retrograde cholangiopancreatography (ERCP) disclosed pancreatic duct invasion over the distal portion of the pancreatic duct with prestenotic dilatation. Liver biopsy showed undifferentiated carcinoma. As suggested by the pathologist, the nasopharyngeal area was checked by the ear, nose and throat doctor, was negative and nasopharyngeal carcinoma was excluded. Therefore, the patient was treated with Gemcitabine (1500 mg/wk), as the suggested treatment schedule, for 24 wk in opioid dependency program. Sequential abdominal CT during follow up showed the disappearance of liver metastasis and shrinkage of the pancreatic tumor. Repeated ERCP after treatment showed re-channelization of the pancreatic duct. During 11 years of follow up, 5 CT scans disclosed not only the disappearance of the hepatic tumor but also no cancer recurrence. Progressive shrinkage of pancreatic head was also noted. Therefore, we can say this malignant case was cured by monotherapy with gemcitabine.

• Gemcitabine
• Gemza
• Cure
• Metastatic hepatic carcinoma
• Undifferentiated carcinoma
• Bone metastasis

The primary tissue-site origin in over 4% of cancers remains uncertain despite thorough clinicopathological evaluation. This study assessed the effect of a Food and Drug Administration-cleared 2,000-gene–expression-profiling (GEP) test on primary tissue-site working diagnoses and management for metastatic and poorly differentiated cancers.

Clinical information was collected from physicians ordering the GEP test for patients with difficult to diagnose cancers. Endpoints included diagnostic procedures, physicians’ working diagnoses and treatment recommendations before and after GEP result availability, and physician reports of the test's usefulness for clinical decision making. Patient date of death was obtained, with a minimum of one year follow-up from date of biopsy.

Sixty-five physicians participated in the study (n=107 patients). Before GEP, patients underwent 3.2 investigations on average (e.g., radiology, endoscopy). Ten immunohistochemistry tests were used per biopsy (SD 5.2). After GEP testing, physicians changed the primary working diagnosis for 50% of patients (95% CI: 43%,58%) and management for 65% of patients (95% CI: 58%,73%). With GEP results, the recommendation for guideline-consistent chemotherapy increased from 42% to 65% of patients, and the recommendation for non-guideline-consistent regimens declined from 28% to 13%. At last follow-up, 69 patients had died, and median survival was 14.0 months (95% CI: 10.2,18.6). Thirty-three percent of patients were alive at 2 years.

In patients with difficult-to-diagnose cancers, GEP changed the working diagnosis and management for the majority of patients. Patients for whom the GEP test was ordered had longer median survival than that historically reported for patients enrolled in treatment trials for cancer of unknown primary.

• autoantibody
• circulating tumor cell
• imaging
• pancreatic cancer
• serological marker
• tumor

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Early Detection of Cancer/methods
• Genetic Markers/genetics
• Humans
• Pancreatic Neoplasms/diagnosis
• Pancreatic Neoplasms/genetics
• Pancreatic Neoplasms/metabolism
• Pancreatic Neoplasms/pathology

• U54 CA163120 NCI NIH HHS
• U01 CA111294 NCI NIH HHS
• R01 CA78590 NCI NIH HHS
• R03 CA139285 NCI NIH HHS
• P50 CA127297 NCI NIH HHS
• R01 CA078590 NCI NIH HHS
• R01 CA131944 NCI NIH HHS
• R21 CA156037 NCI NIH HHS
• R01 CA133774 NCI NIH HHS
• R03 CA 139285 NCI NIH HHS

• Adult
• Aged
• Aged, 80 and over
• Biological Assay
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Decision Trees
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• MicroRNAs/analysis
• MicroRNAs/genetics
• Middle Aged
• Neoplasms, Unknown Primary/classification
• Neoplasms, Unknown Primary/diagnosis
• Neoplasms, Unknown Primary/genetics
• Real-Time Polymerase Chain Reaction/methods
• Sensitivity and Specificity
• Signal Transduction
• United States

Cancer of unknown primary (CUP) is a clinical syndrome representing many types of cancers and diagnoses are typically made after review of clinical presentation, pathology (including immunohistochemical staining) and imaging studies. Treatment with systemic chemotherapy has been shown to result in fairly reproducible objective response rates. Herein, a case of a patient who was initially diagnosed with a poorly differentiated adenocarcinoma of unknown origin is reported. After mRNA gene expression profiling (commercially available CancerTYPE ID), a specific diagnosis of papillary renal cell carcinoma (RCC) was made and then confirmed with additional immunohistochemical staining. The patient was treated with targeted therapy and an objective radiographic response was seen. A literature review suggests this to be the first patient with papillary RCC, identified by molecular profiling, and benefitting from a targeted agent that otherwise would not have been considered in the setting of CUP. This case underscores the importance of considering the use of newer testing technologies in the interest of offering patients more specific, targeted therapy in order to improve efficacy and spare patients toxicities of less specific, empiric chemotherapeutic regimens.

• Cancer of unknown primary
• Gene expression profiling
• Occult primary
• Papillary renal carcinoma

We report a rare presentation of a 66-year-old female with diffuse metastatic adenocarcinoma of unknown primary involving liver, lymphatic system and bone metastases. The neoplastic cells were positive for CK7 and OC125, while negative for CK20, thyroid transcription factor 1, CDX2, BRST-2, chromogranin, synaptophysin, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu). Fluorescence in situ hybridization showed no amplification of the HER2/neu gene. Molecular profiling reported a breast cancer origin with a very high confidence score of 98%. The absence of immunohistochemistry staining for ER, PR, and HER2/neu further classified her cancer as triple-negative breast cancer. Additional studies revealed high expression levels of topoisomerase (Topo) I, androgen receptor, and ribonucleoside-diphosphate reductase large subunit; the results were negative for thymidylate synthase, Topo II-a and O6-methylguanine-DNA methyltransferase. The patient was initially treated with a combination regimen of cisplatin and etoposide, and she experienced a rapid resolution of cancer-related symptoms. Unfortunately, her therapy was complicated by a cerebrovascular accident (CVA), which was thought to be related to cisplatin and high serum mucin. After recovery from the CVA, the patient was successfully treated with second-line chemotherapy based on her tumor expression profile. We highlight the role of molecular profiling in the diagnosis and management of this patient and the implication of personalized chemotherapy in this challenging disease.

• Carcinoma of unknown primary
• Immunohistochemistry
• Molecular profiling
• Triple-negative breast cancer

• Chemotherapy
• Positron emission tomography
• Taxane
• Unknown primary neoplasms

• carcinoma ex pleomorphic adenoma
• carcinoma of unknown primary
• plag1
• salivary gland