Metastatic Adenocarcinoma Of Unknown Origin Research Articles

Value of 18F-FDG PET/CT in the detection of occult malignancy in patients with dermatomyositis

AimDermatomyositis (DM) is an inflammatory myopathy in adults that is strongly associated with malignancy. The aim of this study was to evaluate whether whole-body 18F-FDG PET/CT imaging can offer a standard option searching for underlying malignancy in DM patients. MethodsSeventy-five patients diagnosed with DM were referred to our department for whole-body 18F-FDG PET/CT to determine whether the patients suffered from malignant tumor. All PET images were analyzed by two experienced nuclear medicine physicians separately. ResultsAccording to the 18F-FDG PET/CT results, 19 patients were suspected to suffer from malignant tumor, then biopsy was performed. Of the 19 patients, 17 patients were confirmed to have malignant tumor. The pathological types were: nasopharyngeal carcinoma, rectal cancer, lung cancer, colon cancer, gastric cancer, gallbladder cancer, kidney cancer, ovarian cancer, breast cancer, lymphoma and vertebral metastatic adenocarcinoma of unknown origin. No malignancy was found for the 56 PET-negative patients during follow-up. For the age between 17 patients with malignancy and 58 patients without malignancy, no significant difference was observed. Conclusion18F-FDG PET/CT may be a sensitive and effective method in determining whether the patients with DM suffered from malignant tumor.

SAT-LB102 When the Answer Is Not in the First Look: An Unusual Presentation of Follicular Thyroid Carcinoma

Follicular Thyroid Carcinoma (FTC) accounts for 12% of thyroid cancers. It is most common in women between the ages of 40-60 years old. Although typically diagnosed after incidental palpation or via imaging obtained for other purposes, up to 15% of FTC may exhibit distant metastasis at the time of diagnosis. We present a case which required an interdisciplinary approach to lead to the correct diagnosis. A 49 year-old male presented with an orange-sized lump on his head. He was referred to a tertiary hospital for further evaluation. Brain MRI showed an infiltrative mass within the right parietal bone with extracalvarial, epidural and intraparenchymal extension. He underwent craniotomy for skull tumor resection and pathology revelead a metastatic adenocarcinoma of unknown origin. Pan-CT scanning revealed a 5 cm hypervascular complex nodule in the right thyroid lobe. PET showed uptake in this mass. Fine Needle Aspiration was consistent with FTC. Clusters of tumor cells from the bone surgical sample were positive for CK7, PAX8 and negative for PSA, CK20, PSAP, TTF1, CDX2 and Hepar. After comparison between brain and thyroid samples, a diagnosis of metastatic FTC was corroborated. Foundation testing was sent to guide further therapy. Programmed death-ligand 1 (PD-L1) results were discordant between samples, with the metastatic tissue showing frank 60% positivity, compared to the scant 5% expression at the primary tumor. The most common molecular alterations in FTC are RAS and PAX-8-PPAR gamma1 point mutations. When suspecting a primary tumor of thyroid origin, in the setting of an adenocarcinoma of unknown origin, immunohistochemistry (IHC) is crucial for accurate diagnosis. FTC typically exhibits distinct IHC patterns for markers such as TGB, HBME-1, PAX8, CD-56 and galectin-3. Several characteristics such as degree of angioinvasion and TERT mutations have been linked to greater risks of metastasis and poor prognosis. More recently, PD-L1 was found to be highly expressed in a subset of patients with advanced thyroid cancer, such as follicular and anaplastic thyroid carcinoma. The presence of PD-L1 expression may guide our therapeutic approach towards FTC in the future. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Clear cell carcinoma arising from abdominal wall endometriosis with lymph node metastasis – a rare case report and review of the literature

Abdominal wall endometriosis represents 1-2% of all endometriotic lesions. The malignant transformation of abdominal wall endometriosis is rare, though it can occur. Herein the authors report a rare case of clear cell adenocarcinoma arising from abdominal wall endometriosis with extensive lymph node metastasis. In this case, a 51-year-old woman presented with a growing mass in the right periumbilical area. Computed tomography scan revealed a 5-cm solid mass located on the right rectus muscle. A punch biopsy of the abdominal lesion was performed and histology showed metastatic adenocarcinoma of unknown origin. She had a surgical history of laparoscopic subtotal hysterectomy with right salpingo-oophorectomy. The patient underwent radical excision of the mass, trachelectomy, left salpingo-oophorectomy, and lymph node dissection. The abdominal wall mass showed clear cell adenocarcinoma arising from endometriosis on histology. There were extensive lymph node metastases. The patient underwent adjuvant chemotherapy. Both lymphatic and local invasion are key routes of clear cell adenocarcinoma arising from abdominal wall endometriosis. Extensive lymph node metastasis could be associated with poor prognosis.

Glypican-3 is useful but not superior to Hep Par 1 in differentiating hepatocellular carcinoma from other liver tumours

To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for GPC-3 and Hep Par 1 protein expression by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCCs were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1. This included a case of metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e., a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while those of GPC-3 were 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However, it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilised together with Hep Par 1 as a panel in the diagnosis of HCC.

PTU-159 The Clinical and Service Impact of The National Oesophago-Gastric Cancer Awareness Campaign: A Locality Analysis from County Durham

Introduction The UK national ‘Be clear on cancer (BCOC)’ campaigns led by Public Health England aim to improve public awareness of symptoms of cancer with a view to make an early diagnosis and reduce deaths arising from advanced disease. The 2015 national campaign for oesophago-gastric (OG) cancer ran from 26 January to 22 February with a key message of ‘ Having heartburn, most days, for 3 weeks or more could be a sign of cancer – tell your doctor ’ and a secondary message of ‘ Food sticking when you swallow could be a sign of cancer – tell your doctor .’ The initial analysis of endoscopic outcomes of the national campaign suggested no significant increase in diagnosis of OG cancers. A locality impact analysis has not been reported so far. Methods Aims: This study is aimed as an impact analysis of the BCOC Oesophago-gastric cancer campaign in a specific locality of South Durham Hospitals (Darlington Memorial and Bishop Auckland[DA(CG1]). It aims to assess two aspects of the campaign: (1) clinical gain of a diagnosis of OG cancer and (2) the service impact of the increase in endoscopy demand as 2 WW and routine referrals. Methods: Upper GI endoscopic data was captured from an electronic Endoscopy Scheduling software, as additions to gastroscopy waiting lists at two periods of time: 4 weeks after the OG campaign, in March 2015 and 4 months after the campaign, in July 2015. These included referrals from general practitioners for upper gastrointestinal symptoms in February/March 2015 (to coincide with the campaign period) and June/July 2015 (to coincide with a non-campaign period). Referrals for variceal screening, Barrett’s surveillance, inpatient referrals or patients already known to secondary care were excluded. Of 760 referrals during the two periods, 353 were excluded, leaving 407 true referrals from primary care. Results There were a total of 283 referrals (2 WW-149, urgent-66, routine-69) during the campaign period, which was 2.2 times greater than non-campaign period of 123 referrals (2 ww-79, urgent-9, routine-35). The age distribution of cases was similar during both periods, with patients aged 61–80 having highest referral rates. The median age group of patients referred as 2 ww during the campaign period was 61–70 yrs compared to 71–80 yrs in the non-campaign period (one decade lower). Gender distribution was similar across both periods for 2 ww and routine referrals. However, there were 2.4 times more females referred urgently during the campaign period compared to male patients. During the campaign, despite an increase in referrals, there was no significant increase in OG cancer diagnosis. Only 2 OG cancers (1 oesophageal squamous cell carcinoma, 1 gastric adenocarcinoma) were diagnosed from 2 ww referrals, while none was diagnosed from urgent or routine referrals. These 2 patients presented with dysphagia and weight loss. During the non-campaign period however, 3 malignancies were detected from 2 ww referrals. Only one was an OG cancer (gastric adenocarcinoma), the other two had normal gastroscopies with malignancy detected on imaging (lymphoma, metastatic adenocarcinoma of unknown origin). A total of 10 Barrett’s oesophagus were diagnosed (2.4%), 8 during the campaign period and 2 in the non campaign period. There was no impact on average waiting time from referral to endoscopy for urgent referrals during both periods (29–42 days). The main impact on waiting times was seen for routine referrals: an increase from 29–42 days during non-campaign period to 43–56 days during the campaign period. Conclusion A national Oesophago-gastric cancer awareness campaign produces a significant increase in the number of referrals for gastroscopy, which has an impact on routine waiting times. The campaign has not shown any increase in diagnosis of OG cancers, thereby indicating that other strategies need to be considered for reducing deaths due to these cancers. Disclosure of Interest S. Koo: None Declared, B. Awadelkarim: None Declared, S. Choudhary: None Declared, Y. Viswanath: None Declared, A. Dhar Grant/research support from: Abbvie, Takeda, Shire, Consultant for: Takeda, Abbvie

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Synchronous double primary cancer - intrahepatic cholangiocarcinoma with bone metastases and thyroid carcinoma: A case report.

There is a low incidence of multiple primary cancer, particularly when the cancer is synchronous. The present report presents a case of synchronous double primary malignancies. A 58-year-old woman was admitted to Ling Nan Hospital (Guangzhou, China) complaining of pain in the left hip. X-ray revealed an osteolytic lesion and further examination indicated the presence of double primary cancer, consisting of hepatic cholangiocarcinoma and thyroid carcinoma. Biopsy of the osteolytic lesion showed a metastatic adenocarcinoma of unknown origin. Subsequently, final diagnosis was confirmed by I-131 scan and liver lesion biopsy. The patient received positive multidisciplinary treatments and survived for 9 months following diagnosis. The results of the present case suggest that multiplicity of primary malignancy is not necessarily an indicator of poor prognosis, as long as effective diagnosis and adequate disease management are achieved.

Eyes: Windows to the Soul…or to the Lungs? A Case of Invasive Lung Adenocarcinoma Presenting as Treatment-Resistant Necrotizing Scleritis

INTRODUCTION: Scleritis is often the first clinical manifestation of a systemic disease. Identifying the underlying disease is critical for proper treatment and prognosis. Approximately 43% of scleritis cases are idiopathic, 48% are related to skeletal and connective tissue diseases and 7% are infection related. Malignancy is rarely associated with scleritis. Two previous reports of malignancy (direct scleral involvement with choroidal melanoma and metastatic adenocarcinoma of unknown origin) were associated with an initial presentation of scleritis.

Recurrent Nonhepatic and De Novo Malignancies After Liver Transplantation

After Liver transplantation (LTx), recurrence of hepatic cancer, de novo cancers, and donor-transmitted cancers have been described. However, the data for patients with a prior history of nonhepatic malignancy and its recurrence post-LTx are limited. Aim of this study was to examine the patient with nonhepatic pre-LTx malignancies, and their recurrence post-LTx along with de novo cancers and recurrence of hepatic malignancy in the population. Between March 1996 and July 2006, 1127 patients underwent LTx at our institution. Thirty patients (2.7%) (15 men and 15 women, mean age 56.9+/-12.8 years) had documented nonhepatic malignancies. There were seven colorectal, three prostatic, three cervical, three bladder, six breast, and other nine miscellaneous cancers (one patient had two cancers). Four patients had hepatocellular carcinoma at the time of LTx. All patients were followed up until 2008 with a mean follow-up period of 34.1+/-35.3 months. One patient with oropharyngeal cancer (3.3%), who was recurrence-free pre-LTx for 77.3 months, developed recurrence 36 months post-LTx and subsequently died 11 months postrecurrence. Two patients developed de novo cancer. One developed renal cell carcinoma 46.6 months post-LTx and other developed de novo intra-abdominal metastatic adenocarcinoma of unknown origin. Three of four patients developed recurrent hepatocellular carcinoma. The rate of recurrence of nonhepatic malignancy was 3% and de novo cancer was 6% in the present series. There is a need to develop a guideline for recurrence-free survival period for nonhepatic malignancies before LTx, based on the type and stage of cancer.

Prognostic factors in the diagnostic work-up of cancer patients in an internal medicine department: does age matter?

Increasing life expectancy in the general population has led to a rise in the incidence of cancer and new challenges with regard to the diagnosis, therapy and prognosis of this disease. To assess prognostic factors in the initial work-up of patients ultimately diagnosed with cancer in an Internal Medicine Service, particularly those related with age. A prospective study was undertaken with 224 patients ultimately diagnosed with cancer, as confirmed by histological or cytological study. The neoplasms included respiratory, gastrointestinal, genitourinary, metastatic adenocarcinoma of unknown origin, gynaecological, hepatobiliary and others. Before reaching the diagnosis, the following factors were investigated in all patients: functional status [Karnofsky Performance Status (KPS)], comorbidity (Charlson scale), body mass index (BMI), serum cholesterol and albumin concentrations, cognitive level (Mini-mental test), quality of life (Short Form 36 questionnaire), and extension of the disease according to established criteria. Survival at 1 year was analysed. Statistical analyses were done with spss 11.0 for Windows, using a forward stepwise (likelihood ratio) method to construct the model and a Cox multivariate model for the survival analysis. A total of 224 patients, 167 men (74.5%) and 57 women (25.5%), with a mean age of 66.1 +/- 12.3 years were studied. KPS was >or= 70 in 84% and comorbidity was zero or one in 74%. BMI was 24.25 +/- 4.3, cholesterol 180.7 +/- 4.3, albumin 3.32 +/- 0.5 and Mini-mental score 25.4 +/- 3.7. Metastasis was seen in 131 patients (58.5%) and local disease in 93 cases (41.5%). One-year survival was 38.8% (87 patients) with a mean of 203.8 +/- 143 days. In the Cox analysis, the independent predictive factors for survival were KPS [hazard ratio (HR) = 0.951; 95% CI = 0.930-0.974; p < 0.01], metastatic dissemination (HR = 2.422; 95% CI = 1.643-3.571; p < 0.01), physical quality of life (HR = 0.978; 95% CI = 0.962-0.995; p < 0.01) and albumin (HR = 0.653; 95% CI = 0.455-0.936; p < 0.01). In the initial work-up of patients ultimately diagnosed with cancer in an Internal Medicine Service, functional status, dissemination, the physical component in the quality of life scale and serum albumin levels were independent prognostic factors for survival. Age was not an independent prognostic factor and should not be used as a basis for adopting diagnostic or therapeutic decisions in these patients.

Erlotinib-Associated Acute Pneumonitis: Report of Two Cases

Two cases of erlotinib-associated acute pneumonitis are described. The first patient was started on erlotinib treatment for metastatic non-small cell lung cancer. The second patient was treated with erlotinib for metastatic adenocarcinoma of unknown origin. Both patients developed dyspnea and hypoxemia five to six days after initiation of erlotinib treatment. In both cases, computed tomography scan of the chest showed extensive bilateral ground-glass infiltrates consistent with pneumonitis. In both patients, acute pneumonitis resulted in respiratory failure requiring intubation and mechanical ventilation. Diffuse alveolar hemorrhage was excluded by bronchoscopy in both cases. Bronchoalveolar lavage cultures were negative. Erlotinib treatment was stopped and both patients were treated with corticosteroids. The first patient improved gradually and finally was discharged to a rehabilitation centre, but unfortunately the second patient died of Klebsiella sepsis. Naranjo causality scale in both cases suggested a probable association between erlotinib and pneumonitis. Literature on erlotinib-associated pneumonitis is sparse. The clinical presentation and radiographic findings of erlotinib-associated acute pneumonitis are described.

Markers of Adenocarcinoma Characteristic of the Site of Origin: Development of a Diagnostic Algorithm

Patients with metastatic adenocarcinoma of unknown origin are a common clinical problem. Knowledge of the primary site is important for their management, but histologically, such tumors appear similar. Better diagnostic markers are needed to enable the assignment of metastases to likely sites of origin on pathologic samples. Expression profiling of 27 candidate markers was done using tissue microarrays and immunohistochemistry. In the first (training) round, we studied 352 primary adenocarcinomas, from seven main sites (breast, colon, lung, ovary, pancreas, prostate and stomach) and their differential diagnoses. Data were analyzed in Microsoft Access and the Rosetta system, and used to develop a classification scheme. In the second (validation) round, we studied 100 primary adenocarcinomas and 30 paired metastases. In the first round, we generated expression profiles for all 27 candidate markers in each of the seven main primary sites. Data analysis led to a simplified diagnostic panel and decision tree containing 10 markers only: CA125, CDX2, cytokeratins 7 and 20, estrogen receptor, gross cystic disease fluid protein 15, lysozyme, mesothelin, prostate-specific antigen, and thyroid transcription factor 1. Applying the panel and tree to the original data provided correct classification in 88%. The 10 markers and diagnostic algorithm were then tested in a second, independent, set of primary and metastatic tumors and again 88% were correctly classified. This classification scheme should enable better prediction on biopsy material of the primary site in patients with metastatic adenocarcinoma of unknown origin, leading to improved management and therapy.

Fine-needle aspiration of scalp lesions.

A variety of inflammatory and neoplastic scalp lesions are encountered in surgical pathology. However, the literature on fine-needle aspirations (FNAs) of the scalp is exceedingly rare. We report on a series of 70 FNAs involving cutaneous and subcutaneous lesions on the scalp. A total of 70 fine-needle aspirations of cutaneous and subcutaneous scalp lesions was reviewed to identify patterns of metastasis to the scalp and to demonstrate the effectiveness of FNA in diagnosing these lesions. There were 42 male and 28 female patients, ranging in age from 29-91 yr (mean, approximately 61 yr). Sixty-one patients had a previous history of malignancy. Of these aspirates, 59 were neoplastic, consistent with the patient's known primary. One case was an abscess, and the remaining case was unsatisfactorvy for cytologic evaluation. Follow-up biopsy revealed granulomatous inflammation. The most common primary tumor to metastasize to the scalp was lung carcinoma, which was seen in 18 cases, followed by hematopoietic malignancies in 14 cases. Melanoma was identified in 6 cases, head and neck tumors in 5 cases, renal malignancies in 4 cases, gastrointestinal tumors in 3 cases, sarcoma in 3 cases, breast and prostate malignancy in 2 cases each, and an olfactory neuroblastoma and meningioma in 1 case each. The remaining 9 aspirates were from patients who did not have a previous history of malignancy. These included 6 benign aspirates consisting of 3 epidermal inclusion cysts, 2 lipomas, and 1 neurofibroma. Two aspirates were malignant and included 1 primary squamous-cell carcinoma and 1 metastatic adenocarcinoma of unknown origin. The remaining case was unsatisfactory for cytologic evaluation. Follow-up biopsy of this lesion showed noncaseating granulomas. Of the aspirates from patients with a previous history of malignancy, 97% were neoplastic. Lung carcinoma and hematopoietic malignancies were the most common neoplasms that metastasized to the scalp. Since the scalp is a common site for metastasis, awareness of this fact is useful to both oncologists and dermatologists. It must be understood that FNA can provide a rapid and accurate diagnosis in the evaluation of scalp masses.

Use of tumour marker immunoreactivity to identify primary site of metastatic cancer.

To determine whether variations in the expression of tumour related antigens can predict the origin of tumours. Immunohistological study of tumour marker expression in primary adenocarcinomas and respective metastatic deposits. Antibodies to the following tumour markers were used: polymorphic epithelial mucin (NCRC-11 and SM3), carcinoembryonic antigen, carcinoembryonic antigen with non-specific antigen co-specificity, CA125, CA19.9, prostate specific antigens, and thyroglobulin. Histopathology department of teaching hospital. 100 pathology sections of metastatic adenocarcinoma and their related primary tumours. Concordance of reactivity between primary and metastatic tumours. Reactivity profiles of tumour sites. The correct primary site of origin was predicted in 70% (33/47) of tumours in men and 54% (27/43) tumours in women with antibodies SM3, 288, CA19.9, CA125, and PSA (men only). Specificities ranged from 68% for breast tumour to 98% for prostate tumour. Use of tumour markers in patients presenting with metastatic adenocarcinoma of unknown origin can help localise the probable primary sites and reduce the need for extensive and expensive imaging techniques.

Adenocarcinoma of the vermiform appendix. A population study.

We report seven cases of adenocarcinoma of the vermiform appendix occurring in Iceland during 1974-1989. The patients ranged in age from 25-83 years, mean age 55.1 years. There were five males and two females. Five had mucinous adenocarcinoma, two had adenocarcinoma. Four patients presented with symptoms and signs of acute appendicitis and all had surgically resectable disease. Three of these patients were alive with no evidence of disease four months, two years and 15 years after presentation; one death of disease occurred seven years after ileocecal resection. In three cases, the clinical presentation was that of metastatic adenocarcinoma of unknown origin. Of these patients two were diagnosed at autopsy and one after appendectomy for perforated appendicitis. Survival in this group was six weeks, three months and twelve months, respectively. In none of our patients was the diagnosis made preoperatively and no tumors were found in appendices removed incidental to other intra-abdominal operations. The incidence of adenocarcinoma of the vermiform appendix in Iceland during 1974-1989 was approximately 0.2 cases/100.000/year.

Metastatic lid disease

Metastatic lid disease is a rare cutaneous occurrence presenting as diffuse lid swelling or a localized nodule. The breast in women, the gastrointestinal and respiratory systems in men constitute the commonest primary sites. Lid spread usually occurs late but may occasionally be the first sign of metastasis. The case of a 60-year-old man with upper lid retraction secondary to metastatic adenocarcinoma of unknown origin is presented.

Electron microscopy in determining origin of metastatic adenocarcinomas.

Light microscopy has limited value in predicting where the primary site of a metastatic adenocarcinoma might be located. In our series, electron microscopy was useful in determining the primary site in approximately 85% of patients with a metastatic adenocarcinoma of unknown origin. This study is based on the ultrastructural examination of more than 100 such cases. In the remaining 15% of the cases, electron microscopy usually provided assistance in reducing the differential diagnosis to a minimum, usually to two possible primary sites. The majority of the metastatic adenocarcinomas showed rather specific ultrastructural features to suggest the site of origin. This application of electron microscopy has never been fully explored and has considerable clinical importance and economic impact in health care systems. An extensive work-up to determine the primary site, with its inconvenience to patient and family, as well as delay in adequate treatment, can be avoided with early diagnosis of the primary site.