The role of fine needle aspiration in the diagnosis of thyroid nodules: analysis of 795 consecutive cases.

The utility of fine needle aspiration (FNA) and physical examination for selecting patients with palpable thyroid nodules for surgery was evaluated in 795 consecutive cases. Surgery was performed in 216 patients based upon the cytological diagnosis and clinical criteria. Excluding 42 patients who were lost to follow-up, the remaining 537 were regularly followed up (range, 2-10 years). Cytological findings were classified as malignant, histologic control recommended (suspicious), follicular tumor, benign, and unsatisfactory. Thirty-six aspiration biopsies were positive for malignancy and the diagnosis was confirmed histologically in 34 of them. In 65 patients with final histological diagnosis of malignancy, cytology was positive in 34, suspicious in 20, benign in 3 cases, and unsatisfactory in 8. All patients with cytological diagnosis of follicular tumor had a benign lesion at histology. There were two false positive and three false negative cytological results among the 216 histologically confirmed cases. Excluding unsatisfactory specimen sensitivity, specificity and the predictive value for a positive and a negative result were respectively 95%, 97.5%, 94.5%, and 97%. We conclude that FNA is a very reliable diagnostic test in the evaluation of thyroid nodules and is the best guidance in addition to clinical criteria for selecting patients to be submitted to surgery.     

False-positive and false-negative cases of fine-needle aspiration cytology for palpable breast lesions

Background  Fine-needle aspiration cytology (FNA) is less traumatic and technically easy to apply to small breast tumors. Methods  A total of 382 cases of palpable breast lesions that had undergone fine needle aspiration and histopathologic diagnosis were reviewed with an emphasis on the rate of false positive diagnoses in benign breast lesions. Results  A diagnosis of“malignant”was made in 98 of the 382 specimens (25.6%). The predictive value for malignancy was 97.9%. The sensitivity, specificity, and accuracy of FNA were 86.3%, 98.2%, and 93.2%, respectively, when the“suspicious”group was considered positive for malignancy. The histologic subtypes of the 4 false-positive cases were epithelial proliferative lesions, ductal or lobular hyperplasia. None of these 4 cases were definitely diagnosed as“malignant”by radiological studies. Four false-negative cases by FNA were suspicious for malignancy radiologically. There was no specific pathological subtype associated with false-negative status on FNA in this study. Conclusion  Palpable breast tumors can be definitively diagnosed based on a combination of physical examination, radiological studies and FNA, when the radiological studies concur with the diagnosis by FNA.     

Consumer Beware: A Systematic Assessment of Potential Bias in the Lay Electronic Media to Examine the Portrayal of “PARP” Inhibitors for Cancer Treatment

This study examined how the lay electronic media covers poly-ADP-ribose polymerase, or “PARP,” inhibitors, a class of cancer agents currently under clinical investigation. Of 771 internet links, 51 targeted the lay public. Independent review by two investigators yielded the following categorizations: 36 (71%) were “overly positive”, 15 (29%) “neutral”, and none “overly negative”. “Overly positive” articles used: (l) overstated benefit, (2) included quotations from enthusiastic scientists, and (3) discussed single or small patient subsets. They used such phrases as “the holy grail of cancer research”, “the most exciting development in cancer research in a decade or more…. it could save thousands of lives”, and “we were surprised and delighted…. it’s the kind of thing you don’t really think will happen”. Healthcare providers should be aware of the foregoing when discussing PARP inhibitors—and perhaps other novel therapies—with cancer patients.     

Diagnostic Value of Ultrasound-Guided Fine Needle Aspiration Biopsy in Malignant Thyroid Nodules: Utility for Micronodules

Background: The diagnostic approach to thyroid nodules involves ultrasound-guided fine needle aspirationbiopsy (US-FNAB).We especially aimed to evaluate the contribution and the place of US-FNAB in preoperativeevaluation of the malignant cases and draw attention to discordant cases diagnosed with papillary thyroidmicrocarcinoma (PTMC). Materials and Methods: A total of 276 cases were retrospectively reviewed who weresubsequently diagnosed with a malignancy and who underwent US-FNAB. Results: Some 45 were found to havepreviously undergone the US-FNAB procedure. Of the patients in whom the surgical specimen was diagnosedwith a malignancy, 21 (46.7%) were diagnosed as malignant or suspicious for malignancy, and 24 (53.3%) wereconcluded as benign or insufficient for diagnosis. Patients with the diagnosis of PTMC outnumbering the otherswas a striking finding (11 cases, 24%). Conclusions: We suggest performing repeat aspiration biopsy consideringsampling errors in cases where inconsistency exists between clinical findings and cytological results in thyroidnodules smaller than 10 mm in diameter and with suspicious findings on ultrasonography.     

Cytology in the positive diagnosis and grading of prostatic cancers: which indications do remain at the time of automatic biopsies and endorectal echography?]

The diagnostic sensitivity (Se) and specificity (Sp) of fine-needle aspiration cytology (FNAC) of the prostate can be evaluated by comparing its results to a histological reference: rates of reported Se range from 65-98%, Sp being equal or superior to 95%. Published series are heterogeneous in terms of cancer prevalence, with a 25-85% proportion of histologically proven adenocarcinomas, irrespective of the anatomical stage of the disease. The overall accuracy of screening by core biopsies or FNAC is lower than 5%, and does not justify wide-scale application of these tests. In 75%, cytological assessment of the tumor grade correlates with Gleason's histological score and grade. Severe intraductal dysplasias (DIC 3) are probably involved in some of the cytological grade I cases. Ultrasonographic guidance of FNAC is not recommended in comparison with histologically obtained data. The indications for performing FNAC of the prostate should be different from those of standard biopsies: the former should be carried out on suspicious lesions revealed by digital rectal examination or ultrasonography, or in a staging attempt. FNAC should be reserved for early diagnosis of prostate cancer in patients presenting with non-specific urologic symptoms. Samples should be obtained by digitally-guided transrectal bilateral FNAC.     

Intravenous Leiomyomatosis of the Uterus

Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called “benign metastasizing leiomyoma” and “intracaval mass and cardiac extension”. The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.     

Communicating with Cancer Patients: What Areas do Physician Assistants Find Most Challenging?

Physician assistants (PAs) and other midlevel practitioners have been taking on increasing clinical roles in oncology settings. Little is known about the communication needs and skills of oncology PAs. PAs working in oncology (n = 301) completed an online survey that included questions about their perceived skill and difficulty on several key communication tasks. Overall, PAs rated these communication tasks as “somewhat” to “moderately” difficult and their skill level in these areas as “average” to “good.” Areas of most perceived difficulty were intervening with angry patients or those in denial and breaking bad news. Highest perceived skills were in communicating with patients from cultures and religions different than your own and telling patient he/she has cancer or disease has progressed, and the lowest perceived skills were in discussing do not resuscitate orders. There are areas in which enhancement of communication skills may be needed, and educational opportunities should be developed for PAs working in oncology.     

Cancer-related identity and positive affect in survivors of prostate cancer

Introduction Despite a shift in the cancer culture and language used to describe individuals diagnosed with this disease, the extent to which individuals with cancer adopt a particular cancer-related identity and the impact of these identities in relation to their well-being is virtually unknown. Materials and methods Using a cross-sectional study design and a metropolitan tumor registry, a mail questionnaire to examine post-treatment quality of life was sent to prostate cancer (PCa) survivors. The sample consisted of 490 PCa survivors, ranging in age from 49–88 (M = 69.7; SD = 7.8), one to eight years after diagnosis. The outcome measure used in these analyses was the PANAS to assess positive and negative affect. Results The most frequently reported cancer-related identity was “someone who has had PCa” (57%). The least reported self view was “victim” (1%). Twenty-six percent of men self-identified as “survivors” while 6% thought of themselves as “cancer conquerors.” Only 9% self-identified as a “patient.” Multivariate analyses, adjusted for potential confounders, show respondents who identified themselves as “survivors” or “cancer conquerors” reported significantly higher scores on positive affect than men who self-identified as “patients” (p < .001). Conclusions Although the majority of respondents identified themselves as “someone who has had cancer,” identifying as a “survivor” or “someone who has conquered cancer” appears to have adaptive value for positive mood. Implications for cancer survivors Those who perceive themselves as survivors of prostate cancer may derive some benefit in well-being associated with this self assessment.     

Genetic diagnosis of cancer

The terms “genetic diagnosis” and “presymptomatic/prenatal diagnosis” are often considered synonymous. However, unlike the genetic diagnosis generally invoked in hereditary diseases, “genetic diagnosis of cancer” can mean at least three different types of diagnosis based on genetic methods, in addition to pre-symptomatic/prenatal diagnosis or identification of inherited cancer risk. These three approaches include (1) detection of cancer cells using DNA samples isolated from blood, stool, sputum, or urine; (2) genetic diagnosis of malignancy or benign status; and (3) characterization of individual cancer cells to examine (a) how widely they have spread, (b) whether the tumor is metastatic, and (c) whether the cells are sensitive to anti-cancer drugs or irradiation. Information concerning genetic abnormalities in cancer cells, accumulated in these ways, can be applied to clinical settings where it should provide useful indicators for better management of cancer patients. In this review we discuss recent progress and future prospects for the “genetic diagnosis of cancer.”     

乳腺肿块微血管密度与血氧近红外光参数的相关性研究

Objective: To detect the reliability of near-infrared parameters of blood oxygen of mammary gland phyma from the microvessel density of tumor. Methods; 181 cases of mammary gland phyma who had accepted the examination of the near-infrared TBO-I dual-wave length mammary gland phyma detector were classified by near-infrared parameters of blood oxygen, and were performed the pathologic examination to ascertain whether the tumor was benign or malignant. Among these cases, intratumoral microvessel density of 20 cases of malignant phyma and 20 cases of benign phyma were confirmed by S-P immunohistochemical method, then the relationship between near-infrared parameters and microvessel density were analyzed by medical statistics. Results: (1) The microvessel density and blood concentration of 28 cases of the "high blood" tumor were 24.56 ± 8.110 and 1.891 ± 0.850 respectively. The microvessel density and blood concentration of 12 cases of the "low blood" tumor were 17.98 ± 8.729 and 0.698 ± 0.283 respectively. There was significant difference between the "high blood" and "low blood" tumors (P ＜ 0.05). (2) The intratumoral microvessel density and blood concentration were linearly correlated respectively, and the linear correlation coefficient r = 0.4208 (P ＜ 0.05) in 40 cases of mammary gland phyma.Conclusion: The intratumoral microvessel density and blood concentration of benign or malignant mammary gland phyma were linearly correlated. Blood concentration (one of near-infrared parameters) is reliable to be used as diagnosis criterion of malignant mammary gland phyma.     

Reversible posterior leukoencephalopathy syndrome and anti-neoplastic agents: a review

Reversible Posterior Leukoencephalopathy Syndrome (RPLS) is a well recognized entity with a variety of benign and malignant conditions. Recently it has been found to be associated with the use of anti-neoplastic agents including targeted therapies. RPLS occurs rapidly with the use of some drugs and more slowly with others. Combined therapies are associated with a more frequent and more rapid presentation. This review was based on a literature search for English Language articles concerning RPLS and chemotherapeutic agents published from June 1996 to March 2007. We used the PubMed database with keywords: “RPLS”, “Posterior reversible encephalopathy syndrome”, “(PRES)”, “Chemotherapy” and “MRI”. This syndrome has classical Clinical-Radiologic features that are easy to recognize. Early recognition and withdrawal of the offending agent is all that is needed in most cases. This review highlights the features of the syndrome. It draws our attention to an entity which is being more frequently recognized and whose exact pathologic mechanisms need to be further studied. This syndrome is associated with the use of neurotoxic as well as non-neurotoxic agents and usually runs a benign course if there is an early diagnosis and management.     

Individualization of breast cancer based on histopathological features and molecular alterations

Histopathological findings and molecular alterations well reflect the biological properties of individual primary breast carcinomas. Specifically, pT (size of the invasive component), pN (number of metastatic lymph nodes), histological or nuclear grade, lymphovascular invasion, hormone receptors, and HER2 (c-erbB-2) gene overexpresison or amplification are known to be effective markers for assessing the risk of operable primary breast carcinoma, albeit incompletely. It is expected that additional molecular markers and novel diagnostic tools will be developed in the future to facilitate a more accurate characterization of higher risk node-negative breast carcinomas. This article is based on a presentation delivered at Presidential Symposium 1, “Breast cancer: individualized diagnosis for tailored treatment,” held on 29 June 2007 at the 15th Annual Meeting of the Japanese Breast Cancer Society in Yokohama.     

The effect of WHO reclassification of necrotic anaplastic oligoastrocytomas on incidence and survival in glioblastoma

In 2007 the WHO Classification of Tumours of the Central Nervous System introduced the entity “glioblastoma with oligodendroglioma component” (GBM/OLIGO). This entity accounts for approximately one in every ten new glioblastomas (GBM). In practice, those mixed gliomas with necrosis which were previously diagnosed as anaplastic oligoastrocytoma (AOA) are now designated glioblastoma with oligodendroglioma component. In this way we diagnose as glioblastomas some tumours we already know for which survival is longer than for “classic” glioblastomas. Oncologists should be aware that some newly diagnosed cases of GBM, specifically those called GBM/OLIGO, may behave as AOA. In the next few years we could observe two consequences of this: first, if anaplastic oligoastrocytomas with necrosis are now to be diagnosed as glioblastomas with oligodendroglioma component, obviously it must be expected that the incidence of glioblastoma will increase in these years; second, because these tumours with known longer median OS are now included in the group of glioblastomas, improvement in the survival of patients with glioblastoma in the next few years should be ascribed not only to advances in diagnosis and treatment but also to a semantic factor.     

Histology-Driven Chemotherapy in Soft Tissue Sarcomas

Doxorubicin and ifosfamide are the two chemotherapy drugs that have consistently demonstrated activity in “soft tissue sarcoma” (STS). However, STS is not a homogeneous entity but an umbrella term for a diverse group of more than 40 differing subtypes; each with distinct underlying biology, natural history and response to treatments. The accuracy of the histological and in some cases molecular diagnosis is therefore critical to the optimal treatment of these patients. Leiomyosarcomas have been shown to have limited responsiveness to ifosfamide, but both the combination of gemcitabine and docetaxel, and single agent trabectedin have shown considerable activity in this tumour group. Differences in responses to chemotherapy are seen for leiomyosarcomas of different anatomical sites with uterine leiomyosarcoma demonstrating considerable chemo-responsiveness, whereas vascular leiomyosarcomas appearing far less sensitivity. There is considerable variation in the sensitivity of the three main subtypes of liposarcomas, with well-differentiated liposarcomas showing generalised chemo-resistance through to the impressive responses seen anthracyclines and to trabectedin with the myxoid subtype. Angiosarcomas have demonstrated considerable sensitivity to paclitaxel, a drug that has little activity outside of vascular sarcomas, and liposomal doxorubicin appears to have a particular indication in this subtype. Synovial sarcomas appear to have significant sensitivity to ifosfamide, even on re-challenge. On the other hand, there are subtypes that are chemo-resistant, including gastrointestinal stromal tumour, alveolar soft part sarcoma and clear cell sarcoma, and chemotherapy plays no role in their management. Whilst it is obvious that there is a need to find new agents to treat these tumours, there is an imperative to make sure that the studies that evaluate their “efficacy” are designed to determine the efficacy within differing histiotypes through stratification by histological subtype, or enrichment strategies to ensure that “activity” is not diluted by unresponsive or even chemo-resistant tumour types.     

Separation of the tumor and brain surface by “water jet” in cases of meningiomas

In the surgery of meningiomas one of the most delicate problems is the separation of the tumor from the brain surface. The authors generally recommend microsurgery to preserve the brain surface anatomically and functionally. For this purpose we have developed a new surgical technique according to our concepts of tissue care. After excavating the tumor from inside the tumor brain surface was separated by repeated “water jets” into the tumor arachnoideal space. The “water jet” was produced by an ordinary bulb syringe. The front pressure of the jets was 300–1000 mm of water and the side pressure 100–300 mm of water. In the tumorarachnoideal space the spreading water (phys. NaCl) separates the brain from the tumor with utmost care. We operated on 55 meningiomas of different types with the “water jet” technique. The immediate results were anatomically excellent. Intraoperative and postoperative acute and late edemas appeared only in a few cases. The functions of the nearby brain were generally preserved. The surgery was uneventful when the tumor surface was smooth and the tumor was spherical. When the tumor surface was uneven, one part of the tumor extended under the dura as a thin layer or the tumor was multilobulated with expanded vessels between the lobules, more microseparation was necessary. We compared the results of the “water jet” technique with the results of the “pre-water jet” series. The surgery with the “water jet” technique was much shorter and its results were better than those of microsurgery alone.     

Mixed germ cell tumor and hemangioblastoma in the cerebellum: report of a rare coexistence

We report a case of a cerebellar tumor consisting of a mixed germ cell tumor (GCT) and a hemangioblastoma. A 22-year-old man presented with myoclonus and cerebellar ataxia. Magnetic resonance imaging showed a tumor mass in the left cerebellar hemisphere. The tumor was totally removed, and the histological diagnosis was an undetermined neoplasm. Ten months later, the patient returned with cerebellar hemorrhage at the site of the previous tumor. An emergency craniotomy was performed, and a tumor mass adjacent to the hematoma was resected. Microscopic examination revealed a mixed GCT consisting of a germinoma, choriocarcinoma, and mature teratomatous component. An area of hemangioblastoma was also found in the same tumor mass. A retrospective examination of the histological sample from the first operation indicated a germinoma. A primary GCT of the posterior fossa is very rare, and there are no other reports of the coexistence of a GCT and a hemangioblastoma. A metastatic GCT lesion of extracranial origin should be considered when the intracranial GCT is non-germinomatous and arises in an unusual site. The most probable hypothesis for the histogenesis of this case was a hemangioblastoma complicated by a “tumor-to-tumor” metastatic lesion of testicular GCT with “burnout” of the primary site.     

The role of patient users in cancer genetics services in primary care

There is much research that suggests all aspects of health care in the National Health Service should have patient user experience and input. This is to make sure service provision meets the needs of the local population. The Oldham Cancer Genetics team felt this was very important when developing a new service. Involving “patient users” meant the service kept the “client” at the centre of the planning process. It ensured all locally produced leaflets, family history questionnaires and patient pathways were tailored to the needs of people in Oldham. The “patient users” were invaluable at awareness-raising sessions for both health professionals and Oldhamers as personal experience always offers maximum impact.     

Expression of VEGF and microvessel density in patients with multiple myeloma: clinical and prognostic significance

The conflicting data are reported on the clinical significance of VEGF deregulation and intensity of angiogenesis in multiple myeloma. The aim of this study was to evaluate the incidence and prognostic significance of VEGF expression and microvessel density (MVD) in multiple myeloma, as well as the relationship of their expression with selected clinical data, histological features, and proliferative activity of myeloma cells. We analyzed bone marrow biopsy specimens obtained from 59 patients with newly diagnosed multiple myeloma. Expression of VEGF and MVD was analyzed using standard immunohistochemical method (antibodies against VEGF and CD34, respectively) on B5-fixed and routinely processed paraffin-embedded bone marrow specimens. MVD was estimated by counting the number of microvessels in three “hot spots” at 400× magnification. VEGF immunoreactivity was estimated on the basis of intensity and percentage of positive plasma cells. VEGF was expressed in 47/59 (79.7%) specimens. There was no significant correlation between VEGF overexpression and age, clinical stage, the extent of osteolytic lesions, type of monoclonal protein, hemoglobin concentration, platelet count, serum concentration of creatinine, calcium, and albumins, the extent of bone marrow infiltration, histological grade, and proliferative activity index (measured with Ki-67 immunoreactivity). No significant difference was observed regarding the overall survival between VEGF-positive and VEGF-negative patients (29 vs. 34 months, P = 0.8). Median MVD was 15, ranging from 1 to 89 microvessels per three “hot spots”. There was significant correlation between MVD and histological grade, the extent of bone marrow infiltration, and proliferative activity. Significant difference was observed regarding the overall survival between patients with low MVD (<15) and patients with high MVD (≥15) (46 vs. 22 months, P = 0.009; univariate analysis). The results of this study did not reveal clinical significance of VEGF overexpression in multiple myeloma. On the contrary, the extent of bone marrow angiogenesis is an indicator of biological potency of malignant clone and a predictor of poor survival in newly diagnosed myeloma.     

Patterns of failure after stereotactic radiotherapy of intracranial meningioma

The aim of this work is to evaluate patterns of failure in patients with recurrent meningioma after stereotactic radiotherapy. Of 411 patients with intracranial meningioma treated with radiotherapy at our institution, 22 patients with local tumor progression diagnosed by magnetic resonance imaging (MRI) after radiotherapy (RT) were identified and further investigated. The histologic grade of the meningiomas was World Health Organization (WHO) grade I in 54.5%, WHO grade II in 27.3%, and WHO grade III in 9.1% of cases. Fourteen patients had received fractionated stereotactic RT; five patients underwent intensity-modulated RT. The median total dose was 57.6 Gy at 1.8 Gy/fraction, five times weekly. Local recurrences were divided into the dosimetric categories “central” (“in-field”) and “marginal” (“out-field”). Median follow-up was 59.5 months. Eleven local failures were found to be central, and 11 were marginal. Recurrence-free survival (P < 0.05) and site of local recurrence (P < 0.05) depended statistically significantly on histology. Median recurrence-free survival was 46 months for patients with benign meningioma (WHO grade I) and 31.5 months for patients with higher-grade meningioma (WHO grade II/III). In the WHO grade I group, three recurrences were central and nine were marginal, whereas in the WHO grade II/III group seven recurrences were central and one was marginal. Median time to local tumor progression and site of local recurrence significantly depended on histological grade of meningioma. Regarding site of failure, improvement of dose coverage for benign meningiomas and dose escalation for high-grade tumors might further improve therapy outcome.     

Biological and clinical significance of clonogenic assays in patients with myelodysplastic syndromes

Biological and clinical significance of growth pattern of hematopoietic progenitors were investigated in 117 patients with primary myelodysplastic syndromes (MDSs) at referral. Abnormal (i.e., “leukemic” or absent) growth of GM colonies (CFU-GM) and GM clusters was found in 47% of patients with “advanced” MDS (RAEB, RAEB-t, and CMML) and in 15% of “low-risk” (RA/RARS) patients. In vitro erythropoiesis was decreased in most of the patients, with significantly lower number of BFU-E in “advanced” MDS than in RA/RARS patients. Megakaryocyte progenitors (CFU-MK) were very low or absent in almost all the patients, regardless of the FAB type. Significant correlation was demonstrated between the number of BFU-E and hemoglobin concentration and between number of CFU-MK and platelet count. Growth capacity of GM progenitors appears to be in proportion to “myeloproliferative” capacity of the malignant clone. T-cell depletion had no influence on growth capacity of hematopoietic progenitors, nor did colony growth respond in a dose-dependent manner to different concentrations of LCM. Growth capacity of MDS hematopoietic progenitors was independent of Bournemouth score, of the presence and type of cytogenetic abnormality, and of the expression of CD95 and caspase-3 antigens on bone marrow cells. However, in patients with “abnormal” growth of GM progenitors, CD34 antigen expression was significantly higher than in patients with “normal” growth. “Abnormal” GM growth was found to be independently predictive regarding the survival and the risk for AML development. In contrast, the prognostic value of erythroid and megakaryocyte cultures was found to be limited.