Initial Diagnosis Of Malignancy Research Articles

The incidence and risk factors predictive of bone metastases at initial diagnosis of malignancy.

e18816 Background: Bone metastases are associated with increased morbidity and decreased quality of life in patients with solid tumors. We report here the incidence and predictive factors for bone metastases at initial diagnosis in a large population-based dataset. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients 18 years-old or older and with solid cancers of all stages diagnosed from 2010 to 2019. We calculated the incidence and predictive factors for bone metastases according to demographic and tumor characteristics. Results: Among the 1,132,154 patients identified, 1,075,069 (94.96%) had known bone metastasis status and were eligible for the study. Bone metastases were detected in 55,903 (4.9%) patients. Among patients with bone metastases, the most common primary tumors were lung (44.4%), prostate (19.3%), breast (12.4%), kidney (4.0%), colorectal (2.24%) and pancreas (2.23%). The percentage of bone metastases in patients with non-small cell lung cancer (NSCLC), prostate adenocarcinoma, infiltrating ductal carcinoma of the breast (IDC), and colorectal adenocarcinoma (CRC) was 18.04% (18,123 out of 100,447), 5.92% (9,071 out of 153,325), 2.9% (4,490 out of 154,626), and 1.17% (1,043 out of 89,510) respectively. In addition to T and N stage, independent risk factors by multivariable analysis for bone metastases included female sex and non-squamous histology in NSCLC, black race, hormonal and HER2 status in breast cancer, Gleason score and PSA in prostate cancer, male sex, black race, rectal location, liver metastases and lung metastases in CRC. In univariate analysis, the strongest predictors for bone metastases were N2/3 (28.3%) and T3/4 (24.9%) in NSCLC, T3/4 (15.8%), N2/3 (10.6%), N1 (5.9%) and HER2 positive (4.9%) in IDC, N1 (38.1%), Gleason score 9/10 (22.8%), PSA 98 or higher (19.5%) and PSA 20-97 (16.8%) in prostate cancer, and rectal or rectosigmoid location (1.43% vs 1.05% in colon cancer, p < 0.001) in CRC. Conclusions: Approximately 5% of patients with solid tumors have bone metastases at presentation. In addition to T and N stage, there are several risk factors for bone metastases according to the primary tumor site.

Things We Do for No Reason™: Tumor markers CA125, CA19-9, and CEA in the initial diagnosis of malignancy.

Things We Do for No Reason™: Tumor markers CA125, CA19-9, and CEA in the initial diagnosis of malignancy.

Instant messenger smartphone application for endosonographer/cytopathologist real-time interaction at a distance in EUS-FNA for solid pancreatic lesions.

Background and study aims Telecytopathology (TCP) may allow proper and timely evaluation of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) specimens. The aim of this study was to evaluate the feasibility of TC through a multiplatform instant messenger smartphone application to evaluate specimens of EUS-FNA of pancreatic solid lesions. Patients and methods Twenty-three patients (14 male/9 female; median age: 56 yr.; age range: 33 – 86) with a solid pancreatic lesion were included. Exclusion criteria were as follows: age < 18 yr and predominantly cystic lesions. During each EUS-FNA, after each pass, the aspirated material was spread over a glass slide and was stained by the endoscopist. The glass slide was then reviewed on a microscope with a smartphone fitted in, and the most representative fields were captured and sent to the cytopathologist using WhatsApp Messenger. Results In initial evaluation using TCP rapid on-site evaluation (ROSE), adequate cellularity of the glass slide was detected in 16 of 23 patients (69.6 %). An initial diagnosis of malignancy (positive or suspicious) was possible in 14 of 23 patients (60.8 %). Conclusion The current study demonstrated the feasibility of a low-cost, Internet-based, telecytopathology system using WhatsApp Messenger to provide ROSE of EUS-FNA slides in patients with solid pancreatic lesions.

Mo1291 TELECYTHOPATOLOGY FOR RAPID ON-SITE EVALUATION (ROSE) OF ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE (EUS-FNA) ASPIRATION SPECIMENS OF SOLID PANCREATIC MASS

Telepathology has been defined as a form of communication between medical professionals that includes the transmission of pathology images and associated clinical information for various clinical applications, including diagnosis. ROSE for EUS-FNA of the pancreas provides immediate information regarding cellular adequacy, avoiding repeated procedures and improving diagnosis. However, cytopathologist is not available for ROSE in all endoscopy units. A multi-platform mobile phone application, such as WhatsApp Messenger, could be useful as a tool for TCP, since it could enable remote real-time information exchange, avoiding unnecessary procedures. To evaluate the feasibility and the impact of TCP using WhatsApp Messenger as an auxiliary tool for ROSE in EUS-FNA of solid pancreatic lesions. We prospectively evaluated 20 patients (65% male, median age 57.5 yrs [range 36 to 86]) with pancreatic solid lesions, according to previous CT scans, referred to EUS-FNA. Patients with entirely cystic lesions were excluded. All endoscopic procedures were performed with the patient under conscious sedation with linear therapeutic echoendoscopes (Fujifilm Corporation, EG-53OUT2, Saitama, Japan) and 22G-needles (Expect, Boston Scientific Corporation). After each pass, aspirated material was spread over a glass slide and stained by the endoscopist. The glass slide was then reviewed on a microscope equipped with a mobile phone (Android Platform) in order to capture images. The most representative fields were photographed and sent by WhatsApp Messenger to the cytopathologist. The images were analyzed regarding cellular adequacy of the material and preliminary diagnosis whenever possible. The number of needle passes was determined according to initial evaluation of the cytopathologist. This initial evaluation was compared to the final pathology report (FPR) regarding cellular adequacy and diagnosis. Gold standard for diagnosis of malignancy was surgical report or 12-month follow-up. The endoscopist had training in basic cytology for slide preparing. In the initial evaluation using TCP ROSE, adequate cellularity of the glass slide was detected in 13/20 (65%), vs. 16/20 in FPR (P = 0.37). An initial diagnosis of malignancy was possible in 11/20 (55%) vs, 16/20 (80%) after FPR (P = 0.07). The final diagnosis was malignant in 16/20 (80%). Sensitivity and specificity for diagnosing malignant lesions after FPR were both 100%. The present study demonstrates the feasibility of a low-cost, Internet-based, telecytopathology system using WhatsApp Messenger to provide a rapid on-site evaluation of EUS-FNA slides in patients with solid pancreatic lesions.

Spectrochemical analysis highlights similarities in adenocarcinomas irrespective of primary tissue origins.

e13551 Background: Identification of primary tissue origin of brain metastases can be histopathologically challenging. Initial diagnosis of malignancy can be provided on intraoperative tissue smears; however, it requires formal histopathological examination along with immunohistochemistry to reach a final diagnosis. On occasion this will still fail to determine primary origin. This study aims to demonstrate if Raman spectroscopy is able to determine primary tissue origin of brain metastasis of three common primary tumours. Methods: Formalin fixed paraffin embedded tissue from twenty brain metastasis comprising colorectal adenocarcinomas ( n= 7), lung adenocarcinomas ( n= 7) and melanomas ( n= 6) were obtained from the Brain Tumour NorthWest tissue bank. Sections (10-μm thick) were placed onto glass slides covered in aluminium foil and de-waxed prior to spectral acquisition. 25 spectra per section were collected at random, using a 785 nm laser at 1200 g mm-1grating with an acquisition time of 30 sec. Computational analysis within a MatLab environment was then conducted. Results: Following PCA-LDC analysis, classification accuracy of the three groups was; colorectal adenocarcinoma 71.3%, lung adenocarcinoma 71% and melanoma 70%. A one-way ANOVA showed statistically significant differences between the three groups, p = 0.0014. On combining adenocarcinoma groups accuracy increased to 87.8%, whilst melanoma fell to 68.9%. A student’s t-test confirmed statistical significance between the two groups, p &lt; 0.0001. Conclusions: Raman spectroscopy can classify different tumours by type, though sensitivity and specificity is diminished if used to classify primary tissue origin of adenocarcinomas. Therefore for clinical use, such new tools may aid the clinician to determine tumour type intra-operatively but classic histopathology is still required for tissue origin confirmation. Such technologies may provide a useful adjunct to more conventional approaches; for instance, decreasing the number of immunohistochemical stains required to determine tissue origin. These results also suggest strong similarities between adenocarcinomas of different primary origins.

Predictive Value of Clinical and Laboratory Parameters for Overt Bone Marrow Metastasis in Patients with Solid Malignancy

Bone marrow (BM) metastases are known to worsen the outcome in patients with malignancies and alter the choice of the treatment regimen. In an attempt to identify routine parameters for the prediction of BM metastasis we evaluated the clinical and laboratory data of 103 patients with metastatic solid tumors. We also assessed which of these factors appeared to influence survival. Three laboratory abnormalities were found to be predictive of metastasis on BM biopsy: thrombocytopenia < 50 × 109/L OR 14.4; p = 0.02; hypocellular or dry tap aspirate OR 7.0; p = 0.02 and high serum alkaline phosphatase OR 6.5; p = 0.03. Three additional factors were found to be associated with deceased survival. Thrombocytopenia was associated with decreased survival from a median of 0.8 months to 4.1 months, p < 0.0001. Serum LDH levels more than twice the upper limit of normal were also reduced survival from 1.8 months versus 4.7 months, p = 0.03. Finally, the initial diagnosis of malignancy by bone marrow examination was associated with reduced survival from 1.8 months vs. 4.0 months, p = 0.03 in individuals where BM metastases were not the presenting feature of malignancies. Use of these simple clinical parameters may help in the early diagnosis of bone marrow metastases and improve clinical approach.

Extra cardiac findings in cardiovascular MR: Why cardiologists and radiologists should read together

To assess prevalence and significance of extra cardiac findings (ECF) in clinical routine cardiovascular magnetic resonance (CMR) studies reported by cardiologists alone versus cardiologist and radiologist working together. One-thousand-seventy-four consecutive patients presenting at our institution for CMR work-up of multiple cardiovascular disease entities were enrolled retrospectively in two groups (cardiologists reading alone vs. cardiologists and radiologist reading together). In 1,074 routine CMR studies a total of 357 ECF's were identified in 235 patients yielding a prevalence of 21.9 %. Of these 357 ECF's more than one-third were previously known. In the remaining 223 previously unknown findings 118 (52.9 %) were considered as major ECF's (92 patients), and 105 (47.1 %) were considered as minor ECF's (69 patients). Cardiologists reading alone reported 23 previously unknown ECF's in 23 patients, versus 200 previously unknown ECF in 138 patients by cardiologists and radiologists working together, p < 0.0001. Nevertheless, highly significant ECF's with major prognostic implications, such as the initial diagnosis of malignancy in an individual with no history of cancer, are extremely rare (n = 3, 0.3 %). Cardiologists alone, as well as cardiologists and radiologists working together seem to do well with reporting of such extremely important ECF's. The prevalence of all ECF's was 21.9 %, and 14.9 % of previously unknown ECF's, respectively. However, the prevalence of highly significant ECF's was low. Joint reading with cardiologists and radiologists may increase the number of ECF's detected in CMR studies, but it remains unclear if this could result in an improved long-term outcome of patients undergoing routine CMR.

Dynamic MRI Findings and Clinical Features of Benign Hypervascular Hepatic Nodules in Childhood-Cancer Survivors

The purpose of this study is to investigate the dynamic MRI findings and clinical features of benign hypervascular hepatic nodules in childhood-cancer survivors. We reviewed dynamic MRI findings and clinical features in 15 patients who had been treated for childhood malignant solid tumors and in whom hypervascular hepatic nodules were later found on surveillance imaging by either CT or ultrasound (or both). The benign nature of the lesion was based on histologic examination or clinical and radiologic follow-up (or both). Time between initial diagnosis of malignancy and detection of the hepatic nodule ranged from 4.5 to 13.5 years with the majority of the malignancies being neuroblastoma treated by high-dose chemotherapy and hematopoietic stem cell transplantation. A total of 43 nodules were detected, often multiple and small. Most of the lesions were isointense or slightly hyperintense on T2-weighted imaging and isointense or slightly hypointense on T1-weighted imaging. All nodules had intense enhancement on the arterial phase and were isointense or slightly hyperintense on the delayed phase. A central scar was seen in four. Additionally, hepatic hemosiderosis was noted in four patients, in whom all the lesions were hyperintense on both T1- and T2-weighted imaging. Benign hypervascular hepatic nodules in survivors of childhood malignancy occur years after high-dose chemotherapy and hematopoietic stem cell transplantation. Dynamic MRI findings including intense arterial enhancement and absence of washout in the delayed phase are of great value in the differential diagnosis of these hepatic nodules.

Hypervascular hepatic nodules in childhood cancer survivors: clinical and imaging features

AimThe aim was to review the clinical and imaging features of hypervascular hepatic nodule (HHN) in childhood cancer survivors. Materials and methodsWe retrospectively reviewed 11 pediatric patients (female:male, 7:4; age range, 4.0–12.3 years) who had HHNs detected by surveillance computed tomography (CT) after treatment of a malignant solid tumor and subsequently followed by serial imaging without evidence of recurrent malignancy. The lesions were analyzed in terms of number, size, location, CT and ultrasonographic (US) features, and changes in background liver. In addition, clinical features were investigated along with follow-up changes of HHNs by imaging monitoring. ResultsTime between initial diagnosis of malignancy and HHN occurrence ranged from 3.2 to 8.5 years (median, 5.8 years). Ten patients had received high-dose chemotherapy and autologous stem cell transplantation for advanced neuroblastoma. A total of 22 nodules were detected, being multiple in six patients and measuring 0.5–3.0 cm in size. At sequential postcontrast CT, nodules demonstrated moderate to strong enhancement during the earlier phase and were isoattenuated during the later phase. On US, they appeared as hypo- or isoechoic lesions. During follow-up, 11 nodules (50%) regressed, 6 (27%) progressed, and 5 (23%) remained stable. Additional HHNs were noted in four patients during follow-up. ConclusionChildhood cancer survivors are at risk of developing HHNs, which are often multiple and small, years after completing chemotherapy. They are nonaggressive and tend to have a benign course, making conservative management reasonable.

Diagnosis of Skin Lesions by Trainee Surgeons: Experience Improves Accuracy

Accurate clinical diagnosis depends on the reliable recognition of signs and symptoms. This expertise comes from experience in seeing patients which has been traditionally gained over a long training period. Shortened specialist training (Modernising Medical Careers) has led to a greater reliance on structured teaching and skills transfer programmes. The accuracy of clinical diagnosis and the rate at which diagnostic skills improve during training is important for the assessment of trainees, and the delivery of care. This study assessed the accuracy of clinical diagnosis of skin lesions by two junior plastic surgery trainees. They were asked to diagnose 120 consecutive skin lesions seen in a pigmented skin lesion clinic in 2005, with the histological diagnosis being confirmed following subsequent excision. The process was repeated a year later in 2006 to enable the rate of correct diagnosis to be compared. Initially, 53.3% of diagnoses were correct. A year later, this had risen to 65.0%. Twenty-two different skin pathologies were present in excised specimens, and skin cancers comprised 30%. The trainees demonstrated 93.8% sensitivity in their initial diagnosis of malignancy (95% CI, 79.2-99.2) and 97.4% a year later (95% CI, 86.5-99.9). However, specificity was 69.3% (95% CI, 58.6-78.7) in 2005 and 71.6% (95% CI, 60.5-71.4) in 2006. Accuracy in the diagnosis of the wide range of skin conditions presenting to an out-patient clinic was shown to increase over a 1-year period. We feel that this improvement resulted from regular clinical exposure supported by a structured learning programme. The shortening of the specialist training period may affect the acquisition of diagnostic skills by trainees and impact on the confidence with which they commence consultant practice.

Wie zuverlässig sind unsere Krebsstatistiken?

Among the causes of death, cancer ranks second after cardiovascular diseases. If a cancer patient dies before the tumor is diagnosed the malignancy may be unreported among post-mortem findings and thus is often not included in cancer and cause of death statistics. All 8844 autopsies carried out at the Institute of Forensic Medicine for the City of Hamburg from 1994 to 2001 were analysed and those cases with malignant tumor identified. The cases were then included in the cancer registry if this had not been done previously. The postmortem diagnosis of malignancy was made histologically on formalin-fixed tissue. In these cases attempts were made to find out if the initial diagnosis of malignancy had been made before death. A malignancy was found in 519 autopsies (5.9 %). In 67.3 % of these (349/519) the patients had been aware of the disease. 27.2 % of all malignant tumors (141/519) were discovered during the post-mortem examination. In 5.6 % of cases (29/519) the question of whether the tumor had been diagnosed before death could not be answered because of lack of data or an incomplete case history. In 52.2 % (271/519) of the autopsies the tumor had definitely been the cause of death. Of these 271 tumors 17 % (46/271) were discovered only during the forensic post-mortem examination. The Hamburg Cancer Registry had been notified of only 58 cases of the 519. As a result of this study 451 new cancer cases (86.9 %) were notified to the Hamburg cancer registry. The registration of cancer deaths in Hamburg is incomplete and the notification of cancer to the Cancer Registry is inadequate. The estimated number of unreported cases is probably greater and cancer as the cause of death is higher than reported in the statistics.

Histological validation of diagnoses of thyroid cancer among adults in the registries of Belarus and the Ukraine

In order to evaluate the diagnostic reliability of the thyroid cancers listed in adult registries from the Ukraine and Belarus, a histological review was organised of 327 randomly selected thyroid carcinoma cases diagnosed between 1980 and 1999. A final diagnosis was reached at a 5-day consensus conference by six pathologists who met around a multiheaded microscope. The study concluded with a comparison between the final diagnosis and the initial diagnosis. The pathologists agreed with the initial diagnosis of malignancy in 286 cases (88%). A final diagnosis of papillary, follicular or medullary thyroid carcinoma was reached in 86, 4, and 6% of the cases respectively. In 2.8% of the cases reviewed, diagnostic discrepancies persisted. The percentage of agreement between the final diagnosis and the initial diagnosis was 93%, with a weighted κ-statistic of 0.61 (confidence interval 95% (CI95%): [0.45–0.77]). In all, 89% of the 286 confirmed cancer cases were in agreement for the type of cancer, with a κ-statistic of 0.56 (CI95%: [0.43–0.69]). The level of agreement differed according to cancer categories, with concordance rates of 94, 40 and 33% for papillary, follicular and medullary thyroid carcinomas respectively. The low prevalence of follicular thyroid carcinomas in the adult population studied calls for further exploration. The discrepancies and classification difficulties encountered were analysed.

Soft tissue aspiration cytopathology

Fine-needle aspiration (FNA) biopsy as a diagnostic modality for the pathologic evaluation of soft tissue neoplasms and non-neoplastic soft tissue mass lesions is uncommon and controversial. This procedure contrasts with more traditional diagnostic methods such as marginal excision, incisional (open) biopsy, or even core biopsy to procure tissue from somatic sites. The authors reviewed the results of cytopathologic diagnoses obtained by fine-needle aspiration biopsy over a consecutive 11-month period in patients that presented primarily with a palpable soft tissue mass. A few patients with deep non-palpable soft tissue masses also were evaluated by radiologically guided FNA. Cytopathologic diagnoses were verified by different means including tissue examination either by concurrent cell block or subsequent surgical biopsy, flow cytometry, clinical outcome, or repetition of the FNA procedure. Patients were followed for a minimum of one year to evaluate the mass clinically, to determine whether any further therapy was administered, and to assess disease status. Eighty-two aspirates were performed without complications from 77 patients ranging from 12-88 years of age (mean = 50 yrs.) with men outnumbering women 1.5:1. Soft tissue masses were most common in the extremities (41 cases), followed by the trunk (34 cases), retroperitoneum (5 cases), and head and neck (2 cases). Fine-needle aspirates were diagnosed as malignant in 42 (51%), benign in 32 (39%), nondiagnostic in 6 (7%), and atypical in 2 (2%) cases. Malignant aspirates were comprised of 24 sarcomas (57%), 9 carcinomas (21%), 6 malignant lymphomas (14%), and 3 melanomas (7%). Twenty-two aspirates (52%) had an initial diagnosis of malignancy, whereas 18 (43%) represented metastatic and 2 (5%) recurrent neoplasms. Confirmation of the cytopathologic diagnosis was by concurrent or subsequent tissue examination in 57%, flow cytometry in 5%, clinical outcome in 34%, and repeat aspiration in 4%. One false negative and no false positive diagnoses were issued for a sensitivity and specificity of 100% and 97% respectively in distinguishing benign and malignant lesions by FNA. Of the malignant aspirates, 83% could be subtyped whereas 72% of benign aspirates were correctly subtyped. For primary soft tissue sarcomas, 12 of 19 (63%) were accurately subtyped. In 48% of cases a concurrent cell block was obtained and found diagnostically useful in 54% of them. Aspiration cytopathology of soft tissue mass lesions using FNA biopsy can be an accurate and minimally invasive method for the initial pathologic diagnosis of primary benign and malignant soft tissue masses, for the pathologic confirmation of metastatic tumors to soft tissue, and for the documentation of locally recurrent soft tissue neoplasms. FNA cytopathology is capable of specifically subtyping a large percentage of primary and metastatic soft tissue tumors if cellular material either in the form of a cell block or flow cytometry is obtained in addition to cell smears.

Periosteal Myxoma of the Tibia

Myxoma is one of the rarest benign primary tumors of the long bones. A case of periosteal myxoma of the diaphysis of tibia with a benign course after 7 years, is reported in a 69-year-old man. Radiographic appearance of the lesion showed ero sion of the cortex of bone and extension into soft tissue, suggesting an initial diag nosis of malignancy. A limited biopsy showing benign myxoid tissue was not con sidered specific for diagnosis of myxoma. Histologic examination of the entire lesion was essential to make definitive diagnosis. Differential diagnosis with benign and malignant bone lesions containing myxoid features is discussed. Int J Surg Pathol 2(4) :333-336, 1995

Cellular schwannoma. A clinicopathologic, DNA flow cytometric, and proliferation marker study of 70 patients.

A clinicopathologic study of 70 cases of cellular schwannoma was performed to assess their distribution, response to therapy, and rate of recurrence relative to modern prognostic indicators. Seventy-one cellular schwannomas from 70 patients were retrieved from the files of the Mayo Clinic Tissue Registry. The significance of mitotic index, proliferative marker staining (proliferating cell nuclear antigen and MIB1), immunochemical p53 expression, and DNA ploidy were assessed relative to tumor behavior, particularly recurrence. All parameters were subject to statistical analysis (Student's t test). Cellular schwannomas represented 4.6% of benign peripheral nerve tumors operated on at the Mayo Clinic. In 15% of the cases, an initial diagnosis of malignancy had been made. The median patient age was 47.7 years (range, 15-80 years) and the female-to-male ratio was 1.6:1. The principle tumor locations were the para- and intraspinal regions, including the sacrum (64%), extremities (25%), and intracranial space (8%). All tumors consisted primarily of hypercellular, compact, Antoni A tissue. Mitoses (< or = 4/10 hPF]) were observed in 71% of the cases. Foci of necrosis were noted in 11% of cases. Ultrastructural studies and immunohistochemistry clearly demonstrated features of schwannian differentiation. Surgery was the treatment in all cases. Excision was intralesional to gross total in the majority; total resection with wide margins was undertaken in three tumors, each of which had initially been considered malignant. Follow-up in 47 patients (67%) ranged from 1 to 29 years (mean, 7.7 years) and revealed recurrences in 11 patients (23.4%): no patient experienced metastasis or died of tumor. Although no correlation existed between recurrence and DNA ploidy, percent S-phase determinations, proliferation marker (PCNA, MIB1) staining, or the frequency of p53 immunoreactivity, a statistically significant correlation (P < 0.001) was observed, however, between recurrence and mitotic indices. Proliferation indices, as defined by immunochemical analysis, are not useful predictors of recurrence in cellular schwannoma. In lesions not completely resected, tumor recurrence is significantly correlated with mitotic count. The significant overall frequency of recurrence in this series is attributable to a high proportion of intraspinal and intracranial tumors. Our study confirms the benign nature of cellular schwannoma and underscores the necessity of distinguishing them from malignant peripheral nerve sheath tumors, lesions that often require adjuvant therapy.