Adenocarcinoma Of Unknown Primary Site Research Articles

Risk factors and predictors for tumor site origin in metastatic adenocarcinoma of unknown primary site.

BackgroundMetastatic adenocarcinoma of unknown primary site (MACUP) is the most common cancer of unknown primary site, and shows worse prognosis. Prediction of its tumor site origin attracts a growing attention. However, the site determined by gene expression profiling does not have a significant impact on the survival. Some other special method might need to be found out.MethodsWe reviewed 1011 MACUP patients diagnosed by pathological examination and immunohistochemistry based on the Surveillance, Epidemiology, and End Results (SEER) database during 2010–2016. Kaplan–Meier curves and Cox proportional hazard model were analyzed to compare the survival. Logistic regression models and relevant nomograms were performed to predicting the probability of the primary site which including digestive system, respiratory system, and female breast. The validation and clinical utility of models were measured with relevant statistical approaches.ResultsAbout 324 (32.1%), 299 (29.6%), and 203 (20.1%) of MACUP patients were identified as the primary sites of digestive system, respiratory system, and female breast, respectively. Patients derived from digestive system and respiratory system showed poorer survival than these with other sites. Digestive system was significantly associated with liver (Odds ratio =13.21 [95% confidence interval =8.48–21.02]) or lung (2.36 [1.40–3.97]) metastasis, while respiratory system was linked to brain (11.68 [6.68–21.26]) or lymph node (3.39 [2.26–5.13]) metastasis. Patients identified as female breast were prone to occur bone metastasis (5.85 [3.68–9.45]). Logistic regression nomograms were developed to help clinicians intuitively predict the probabilities of tumor site origin with 0.867, 0.824, and 0.753 of the C‐index, respectively. Decision curve analysis and clinical impact curves both revealed the clinical effectiveness.ConclusionsWe profiled different tumor site origin of MACUP patients and established prediction models. These features might be significant for clinicians to improve the probabilities of predicting the primary sites, and to decide subsequent treatment strategy.

The diagnostic Value of Cadherin 17 & CDX2 Expression as Immunohistochemical Markers in Colorectal Adenocarcinoma

Abstract Background & Objective Colorectal cancer is a major cause of morbidity and mortality throughout the world. In Egypt, it is the seventh commonest cancer representing 3.47% of male cancers and 3% of female cancers. Although the diagnosis of colorectal cancer is straight forward in primary site, yet it may represent a diagnostic problem in metastatic tumour of unknown primary origin. Pathologists are often called upon to suggest a site of origin in patients with metastasis of an unapparent primary tumour site. This is because some specific tumour types may respond well to targeted molecular therapies. Most tumours of unknown primary site are evaluated with immunohistochemical analysis in combination with morphologic assessment and correlation with clinical data. Therefore, establishment of reliable diagnostic markers that confirm or rule out colorectal origin are mandatory especially in adenocarcinomas of unknown primary site which is one of the most clinical problems. The aim of this work is to study the expression of Cadherin 17 & CDX2 in colorectal carcinoma to evaluate their roles when metastatic colorectal carcinoma is suspected in cancer of unknown primary site. Material & Methods This retrospective study included (65) cases of adenocarcinomas: 35 cases of colorectal adenocarcinoma (whether primary or metastatic) and 30 cases of non colorectal adenocarcinoma from other different sites. Our cases were retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from (2010 to 2015). Immunohistochemical study was performed using monoclonal cadherin 17 & CDX2 antibodies. Results The sensitivity of CDX2 and cadherin 17 were 97.1% and 100% respectively in detecting colonic adenocarcinoma. The specificity of CDX2 was 53.3% while cadherin 17 showed a specificity of 50%. The PPV, NPV and overall accuracy of CDX2 versus cadherin 17 were 70.8%, 94.1% and 76.9% versus 70%, 100% and 76.9% respectively. Conclusion Cadherin 17 is a more sensitive marker than CDX2 in diagnosis of carcinoma of unknown primary site especially when colorectal carcinoma is suspected.

Peritoneal carcinomatosis of unknown primary site may be an undiagnosed appendiceal adenocarcinoma. A case series

BackgroundPeritoneal carcinomatosis is sometimes diagnosed by cytology or by biopsy, but routine radiologic and endoscopic workup may not reveal a primary site. This clinical condition is called adenocarcinoma of unknown primary site. MethodsThe clinical findings of two patients with adenocarcinoma of unknown primary site were presented and the implications for management of similar patients were suggested. ResultsThe patient had the diagnosis of adenocarcinoma of unknown primary site made when cancer was discovered at the time of umbilical hernia repair or laparoscopy. Radiologic and endoscopic tests were not definitive in providing the primary site for the malignancy. Exploratory laparotomy was performed which revealed an appendiceal mucinous adenocarcinoma as the cause of the peritoneal carcinomatosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) were used at the time of the exploratory laparotomy to treat the appendiceal adenocarcinoma with peritoneal metastases. ConclusionsPeritoneal carcinomatosis of unknown primary site may be caused by an occult appendiceal adenocarcinoma. This error in diagnosis may lead to suboptimal treatment. Surgical exploration to visualize a normal appendix should occur prior to making a definitive diagnosis of peritoneal carcinomatosis of unknown primary site.

Clinical pharmacodynamic/exposure characterisation of the multikinase inhibitor ilorasertib (ABT-348) in a phase 1 dose-escalation trial

BackgroundIlorasertib (ABT-348) inhibits Aurora and VEGF receptor (VEGFR) kinases. Patients with advanced solid tumours participated in a phase 1 dose-escalation trial to profile the safety, tolerability, and pharmacokinetics of ilorasertib.MethodsIlorasertib monotherapy was administered at 10–180 mg orally once daily (Arm I, n = 23), 40–340 mg orally twice daily (Arm II, n = 28), or 8–32 mg intravenously once daily (Arm III, n = 7), on days 1, 8, and 15 of each 28-day cycle.ResultsDose-limiting toxicities were predominantly related to VEGFR inhibition. The most frequent treatment-emergent adverse events ( > 30%) were: fatigue (48%), anorexia (34%), and hypertension (34%). Pharmacodynamic markers suggested that ilorasertib engaged VEGFR2 and Aurora B kinase, with the VEGFR2 effects reached at lower doses and exposures than Aurora inhibition effects. In Arm II, one basal cell carcinoma patient (40 mg twice daily (BID)) and one patient with adenocarcinoma of unknown primary site (230 mg BID) had partial responses.ConclusionsIn patients with advanced solid tumours, ilorasertib treatment resulted in evidence of engagement of the intended targets and antitumour activity, but with maximum inhibition of VEGFR family kinases occurring at lower exposures than typically required for inhibition of Aurora B in tissue.Clinical Trial Registration: NCT01110486

Left Supraclavicular Lymphadenopathy as the Only Clinical Presentation of Prostate Cancer: A Case Report

Abstract Prostate cancer usually metastasis to the regional lymph nodes and can rarely metastases to nonregional supradiaphragmatic lymph nodes. Cervical lymph node metastasis of prostate cancer is extremely rare. However, it should be considered in the differential diagnosis of cervical lymphadenopathy in male patients with adenocarcinoma of unknown primary site. In this report we present a rare case of metastatic prostate adenocarcinoma with left supraclavicular lymphadenopathy as the only clinical presentation with no other evidence of metastasis to the regional lymph nodes or bone metastasis.

Liver metastases from adenocarcinomas of unknown primary site: management and prognosis in 68 consecutive patients.

In this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides survival rates, treatment outcomes, and prognostic factors. In all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma. Median age was 61 years (29-90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3%) patients whilst 66 patients (97%) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7%), lungs (32.4%), bones (25%), peritoneum (11.8%), brain (4.4%), and adrenal glands (2.9%). Of all 68 patients, 39 (57.4%) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy [12.5 months (95% CI 8.3-16.7) vs. 4 months (95% CI 1.2-6.8), (p = 0.026), respectively]. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (p = 0.009), chemotherapy (p = 0.024), serum albumin (p = 0.012), and serum CA 19-9 level (p = 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP. Patients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors.

2212 Liver metastases from adenocarcinomas of unknown primary site: Management and prognosis in 68 consecutive patients

2212 Liver metastases from adenocarcinomas of unknown primary site: Management and prognosis in 68 consecutive patients

Comprehensive Genomic Profiling of Carcinoma of Unknown Primary Site: New Routes to Targeted Therapies.

For carcinoma of unknown primary site (CUP), determining the primary tumor site may be uninformative and often does not improve outcome. To discover opportunities for targeted therapies in patients with CUP not currently searched for in routine practice. Comprehensive genomic profiling on 200 CUP formalin-fixed paraffin-embedded specimens (mean, 756× coverage) using the hybrid-capture-based FoundationOne assay at academic and community oncology clinics. Presence of targetable genomic alterations (GAs) in CUP and responses to targeted therapies. There were 125 adenocarcinomas of unknown primary site (ACUPs) and 75 carcinomas of unknown primary site without features of adenocarcinoma (non-ACUPs). At least 1 GA was found in 192 (96%) of CUP specimens, with a mean (SD) of 4.2 (2.8) GAs per tumor. The most frequent GAs were in TP53 (110 [55%]), KRAS (40 [20%]), CDKN2A (37 [19%]), MYC (23 [12%]), ARID1A (21 [11%]), MCL1 (19 [10%]), PIK3CA (17 [9%]), ERBB2 (16 [8%]), PTEN (14 [7%]), EGFR (12 [6%]), SMAD4 (13 [7%]), STK11 (13 [7%]), SMARCA4 (12 [6%]), RB1 (12 [6%]), RICTOR (12 [6%]), MLL2 (12 [6%]), BRAF (11 [6%]), and BRCA2 (11 [6%]). One or more potentially targetable GAs were identified in 169 of 200 (85%) CUP specimens. Mutations or amplifications of ERBB2 were more frequent in ACUPs (13 [10%]) than in non-ACUPs (3 [4%]). Alterations of EGFR (10 [8%] vs 2 [3%]) and BRAF (8 [6%] vs 3 [4%]) were more common in ACUPs than in non-ACUPs. Strikingly, clinically relevant alterations in the receptor tyrosine kinase (RTK)/Ras signaling pathway including alterations in ALK, ARAF, BRAF, EGFR, FGFR1, FGFR2, KIT, KRAS, MAP2K1, MET, NF1, NF2, NRAS, RAF1, RET, and ROS1 were found in 90 (72%) ACUPs but in only 29 (39%) non-ACUPs (P < .001). Almost all CUP samples harbored at least 1 clinically relevant GA with potential to influence and personalize therapy. The ACUP tumors were more frequently driven by GAs in the highly druggable RTK/Ras/mitogen-activated protein kinase (MAPK) signaling pathway than the non-ACUP tumors. Comprehensive genomic profiling can identify novel treatment paradigms to address the limited options and poor prognoses of patients with CUP.

A Case of Pulmonary Tumor Thrombotic Microangiopathy Caused by Adenocarcinoma of Unknown Primary Site

A previously healthy 59-year-old man presented with a 2-month history of exertional dyspnea and dry cough. He had been admitted to a nearby hospital because of advanced dyspnea. Echocardiography indicated pulmonary hypertension, and perfusion images showed multiple subsegmental defects. The patient was diagnosed with a pulmonary embolism, and anticoagulation therapy was initiated. However, the symptoms worsened, and he was referred to our hospital with shock and respiratory failure. Right heart catheterization demonstrated mean pulmonary arterial pressure (mPAP) of 58mmHg and cardiac index (CI) of 1.8L/min/m2.

Concurrent pleural infiltration by chronic lymphocytic leukemia and adenocarcinoma of unknown primary site diagnosed by effusion cytology

Synchronous malignancies in a pleural effusion are rare. A case of concurrent pleural infiltration by adenocarcinoma of unknown primary site and chronic lymphocytic leukemia (CLL) is presented in this case study, which was diagnosed by effusion cytology. Pleural effusion is not an uncommon complication in patients with B-CLL. Even in a pleural effusion rich in monoclonal lymphocytes, the presence of a second cancer must be excluded because this can be the main cause of mortality. The role of cytology in such cases is of paramount importance.

Pituitary metastasis from adenocarcinoma

. CASE A 50-year-old male patient sought medical care com -plaining of cephalalgia for 4 months, diplopia and ptosis of the left eyelid for 30 days. He reported loss of libido and erectile dysfunction in the previous six months. He was before a salutary individual. Physical examination: body mass index (BMI) 24, with ptosis and ophthalmo-plegia of the left eye, arterial pressure of 140/80 mmHg. No other alterations. Magnetic resonance imaging (Figure) showed hetero -geneous mass into the sella turcica with suprasellar ex-tension, causing displacement of optic chiasm and third ventricle floor, with intense opacification after contrast.The laboratory exams showed normal thyroid func-tion, low levels of gonadotropins and total testosterone, normal levels of basal cortisol and IGF-1 and very small increase in serum prolactin. Renal function, serum so-dium and urine density were within normal limits. Cen -tral hypogonadism and slight hyperprolactinemia were de -tected, without evidence of posterior pituitary alteration. An endoscopic transsphenoidal pituitary surgery were performed and anatomopathological exam showed metastasis of moderately differentiated adenocarcinoma of unknown primary site. Postoperative exams showed anemia, increased GGt, FA and CA 19-9. Immunohisto -chemical analysis indicated origin in the gastrointestinal tract, imaging of thorax and abdomen showed lymphade -nopathies and small irregularities on the antral mucosa wall of the stomach. Upper gastrointestinal endoscopy with biopsy showed stomach antral adenocarcinoma.DISCUSSIONMetastatic tumors of the pituitary gland are rare complications

Primary hepatic neuroendocrine carcinoma with nonbacterial thrombotic endocarditis: A case report

Nonbacterial thrombotic endocarditis (NBTE) is occasionally found in patients with carcinoma (lung or gastrointestinal) or debilitating diseases. Definite diagnosis of NBTE should be performed by autopsy. It is difficult to diagnose NBTE if patients have no clinical signs of thromboembolism. Here, we present a case of primary hepatic neuroendocrine carcinoma with NBTE as proven by autopsy.

Rare form of extraovarian peritoneal serous papillary carcinoma with solitary tumor in the abdominal wall: A case report and literature review

Cases of cancer presenting with microscopically confirmed metastatic malignancies for which no primary site can be detected are a challenge to stage clinically. Adenocarcinoma of unknown primary site is a subtype with high frequency that has no standard treatment and a poor prognosis. A 32-year-old female was found to have a tumor in the abdominal wall. Tumorectomy was conducted. A pathological examination indicated serous papillary adenocarcinoma, and peritoneal or ovarian cancer was suspected. Exploratory laparotomy and partial resection of the ovaries were carried out, but there were no malignant findings in the peritoneum, ovarian tissue or ascitic fluid. This is an extremely rare case of serous papillary adenocarcinoma with a cystic tumor that was categorized as extraovarian peritoneal serous papillary carcinoma (EPSPC) without other clinical findings.

Large Mass Affecting Retroperitoneal Great Vessels: A Rare Presentation of A Cancer of Unknown Primary with Diagnostic Dilemma and Challenged Surgical Intervention

Cancers of unknown primary site (CUPs) consist of a clinical entity which accounts for 3-5% of all solid tumor patients. They are metastatic solid tumors whose fundamental characteristic is the absence of identifiable site of the primary tumor. We report the case of a completely asymptomatic 34-year-old man with a palpated huge mass found incidentally in the left abdomen. All the investigations were normal. During the operation, a large mass was identified 2 cm below the left renal artery which was displacing and encompassing the great retroperitoneal vessels and the left ureter. A complete resection of the mass was performed while the histological examination revealed a solitary retroperitoneal lymph node categorized as metastatic adenocarcinoma of unknown primary site. It is essential to assess the high incidence of patients with cancer who present with CUP. Early surgical excision of the metastatic lesion followed by adjuvant combination chemotherapy should be considered for patients with only a single site of malignancy.

Subcutaneous Fat Necrosis as the Presenting Feature of a Pancreatic Carcinoma

The association between pancreatic panniculitis and pancreatic disease is well described, but differentiation among the neoplastic causes of the syndrome remains difficult due to substantial overlap in histological and immunohistochemical features. We report a case of subcutaneous fat necrosis as the presenting feature in a 61-year-old man with metastatic carcinoma of pancreatic origin. Previous pathological evaluation of the patient's liver biopsy led to an initial diagnosis of adenocarcinoma of unknown primary site. One month later, the patient presented with pancreatic panniculitis, prompting further investigation. Immunohistochemistry was consistent with neuroendocrine differentiation, but the patient rapidly decompensated and died before the evaluation was complete, leaving the definitive diagnosis in question. In our review of the published reports of tumor types associated with pancreatic panniculitis, we found that immunohistochemical staining and electron microscopy can and should be used in conjunction with clinical correlation to accurately differentiate neuroendocrine tumors from carcinomas with acinar cell features. Accurate diagnosis of these tumors is necessary to determine prognosis and define appropriate therapy.

Therapy of Adenocarcinoma of Unknown Primary: Are We Making Progress?

Therapy for patients with unknown primary carcinoma is evolving and requires a detailed understanding of the various clinicopathologic subsets with more favorable prognoses. For the remainder, and most patients with unfavorable prognoses, data on current empiric chemotherapy with the newer drugs seems to show improved overall survival compared with older historical data, including comparisons with large retrospective series and prospective phase II trial results. Several recent clinical trials have recently documented long-term survival for a minority of patients. The survival of patients with several metastatic adenocarcinomas of known primary sites, including colon/rectum, lung, and pancreas, has been improved by the administration of chemotherapy alone or combined with biologic targeted drugs (bevacizumab, erlotinib). Approximately 60% of the patients with unknown primary adenocarcinoma have clinically occult primary sites of colon/rectum, lung, and pancreas. Many of these patients will also benefit from therapeutic regimens now proven to be useful for patients with these known primary sites. All available data make a convincing argument that progress is being made for the commonly seen patients with adenocarcinoma of unknown primary site, and is likely to continue as understanding of these and other neoplasms further evolves.

The value of calretinin and cytokeratin 5/6 as markers for mesothelioma in cell block preparations of serous effusions

To determine the value of calretinin and cytokeratin (CK) 5/6 in discriminating mesothelioma from adenocarcinoma in serous effusion specimens. A total of 101 recent, histologically or clinically confirmed malignant effusions with immunostained cell block preparations were reviewed. The cases consisted of 34 mesotheliomas and 67 adenocarcinomas. This included 17 ascitic fluid and 84 pleural fluid samples. The adenocarcinomas included metastatic carcinomas from the breast (12), lung (19), stomach (3), colon (1), pancreas (2), ovary (6) endometrium (1) and 23 histologically confirmed metastases from unknown primary sites. The cases were assessed as negative or positive (>5% of cells stained). The staining pattern was recorded as cytoplasmic, cell membrane, nuclear or cytoplasmic and nuclear staining. Calretinin staining was present in 97% (33/34) of the mesothelioma cases with a majority of them showing both cytoplasmic and nuclear staining (29/33). Only 3% (2/67) of adenocarcinomas were positive for calretinin, one being a lung adenocarcinoma and the other an adenocarcinoma of unknown primary site in an ascitic fluid. Cytokeratin 5/6 staining was also present in 33/34 (97%) of mesothelioma cases. Six (9%) adenocarcinomas were positive, including metastases from the lung (1), breast (1), ovary (2) and unknown primary site (2). Four of the six adenocarcinoma cases positive for CK5/6 were in ascitic fluids. No cases of mesothelioma were negative for both calretinin and CK5/6. Only one adenocarcinoma case, (which was from unknown primary site in an ascitic fluid sample), was positive for both markers. The results confirm that calretinin and CK 5/6 are useful markers for mesothelioma in effusion specimens. CK5/6 staining may be less useful for peritoneal fluid specimens where metastatic adenocarcinomas may be more likely to express the antigen. Further study of ascitic/peritoneal specimens is warranted. However, positive staining, particularly for both antigens, is highly indicative of a mesothelial origin for cells. The two markers make a useful addition to EMA and the panel of adenocarcinoma markers routinely applied to effusion specimens.

Metastatic adenocarcinoma of unknown primary site

Metastatic adenocarcinoma of unknown primary site

Differentiation Between Pancreaticobiliary and Upper Gastrointestinal Adenocarcinomas

Metastatic adenocarcinoma of unknown primary site, eg, to lymph nodes, liver, or lung, may originate from many organs. Microscopic differentiation of adenocarcinomas from the pancreaticobiliary and upper gastrointestinal tracts may be difficult because of shared histologic and immunohistologic features. A high prevalence of cytokeratin (CK)17 expression in pancreaticobiliary adenocarcinoma was reported, and preliminary data indicate infrequent or missing expression in gastric adenocarcinoma. The prevalence of CK17 expression in gastric cardiac and esophageal adenocarcinomas has not been studied. We studied CK17 expression in tissue microarrays of 67 distal gastric, 71 gastric cardiac, and 46 esophageal adenocarcinomas and compared it with expression in 55 pancreatic, 23 extrahepatic bile duct, and 49 colorectal adenocarcinomas. CK17 expression was as follows: pancreatic, 88%; bile duct, 59%; esophageal, 30%; distal gastric, 28%; gastric cardiac, 27%; and colorectal adenocarcinoma, 6%. These differences were statistically significant for all tumor types except in comparisons of esophageal, cardiac, and distal gastric adenocarcinoma. The prevalence of CK17 expression in pancreatic and extrahepatic bile duct adenocarcinomas is substantially higher than in upper gastrointestinal tract and colorectal adenocarcinomas. However, in individual cases of adenocarcinoma of unknown primary site, CK17 results alone are insufficient to differentiate the analyzed tumor entities.

Metástasis cutáneas de adenocarcinoma de origen primario desconocido

Metastatic cancer of unknown primary site appears in 5-10% of oncologic patients. The primary tumor is usually discovered at autopsy and only in 27 % of patients alive. Metastases from cancer of unknown primary site may be located in the skin and subcutaneous tissue and it is the dermatologist the first in evaluating these patients. We present a case of cutanoeus metastases from moderately-differentiated adenocarcinoma of unknown primary site. The immunohistochemical study revealed positive staining for CEA and negative staining for PSA. The primary tumor could not be identified in spite of the imaging and endoscopic studies performed. Based on these studies we excluded a colorectal or prostatic origin and considered a pancreatic adencarcinoma as the possible primary tumor. Even though a minority of these patients will have a curable disease, the appropiate use of pathological diagnosis and selected imaging studies for an optimal management of patients with a tumor of unknown primary site should not be ignored.