Deauville Scores 4 or 5 Assessed by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Early Post-Allotransplant Is Highly Predictive of Relapse in Lymphoma Patients

The impact of early fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT) status on survival after allogeneic transplantation for lymphoma is poorly reported. This retrospective study included all adult Hodgkin lymphoma (HL) or non-Hodgkin lymphoma(NHL) patients (>18 years old) who benefited from FDG PET-CT before (within 1 month) and/or early (+3 months and within +6 to 9 months) after allogeneic stem cell transplantation in our institution between 2005 and 2015 and who were still without documented progression or relapse at the time of the FDG PET-CT. All FDG PET-CT were reviewed by a nuclear medicine expert in hematology and restaged according to the Deauville scale. FDG-PET CT was considered positive when the uptake was higher than liver background (Deauville score ≥ 4). The primary objective was to study the impact of pre- and post-transplant FDG PET-CT on lymphoma-free survival (LFS) and overall survival (OS). Inclusion criteria were fulfilled for 103 patients (69 men; median age, 51.6 years old; range, 22 to 67). Diagnoses were high-grade NHL (n = 47), low-grade NHL (n = 6), T cell lymphoma (n = 34), and HL (n = 16). More than half of the patients were in complete remission at the time of transplant (n = 56). A reduced-intensity conditioning regimen was applied in most cases (n = 90). With a median follow-up of 49.5 months (range, 6 to 140.5) for alive patients, median 3-year OS and LFS were, respectively, 81% (range, 71% to 87%) and 65% (range, 54% to 74%) for the entire cohort. In multivariate analysis, positive FDG PET-CT at 3 months was the strongest independent factor significantly associated with poorer LFS (hazard ratio, 9.22; 95% confidence interval, 1.88 to 645.2; P = .006). FDG PET-CT positivity at 3 months appears to be highly predictive of LFS in patients after allogeneic transplantation and may help to guide strategies to prevent relapse. These results need to be validated prospectively.     

Radiologic and Clinical Predictors of Malignancy in the Follicular Lesion of Undetermined Significance of the Thyroid

Various ultrasonographic characteristics of thyroid nodules have been associated with a higher likelihood of malignancy, and certain clinical features may also increase the likelihood of malignancy in patients. This study is designed to determine the ultrasonographic and clinical predictors of malignancy in the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category. A search through the cytology files at our institution was made for cases with diagnosis of AUS/FLUS. The clinical and radiologic findings were correlated with the final surgical pathology diagnosis. A total of 140 cases of AUS/FLUS with corresponding surgical intervention were identified (112 females and 28 males). There was a 79 % malignancy rate in nodules with irregular contours, compared to 51 % in nodules with regular outlines. Nodules demonstrating calcifications showed a 57 % malignancy rate, compared to 50 % in nodules without calcifications. Sixty-one percent of cases with an ultrasonographic diagnosis of indeterminate to suspicious were malignant following surgical resection. The rates of malignancy in patients with radiation exposure, symptomatic nodules, and positive family history of thyroid cancer were 22, 59, and 33 %, respectively. BRAF mutation was demonstrated in 57 % of malignant cases and in none of benign cases. No single clinical or ultrasonographic feature or combination of features is adequately sensitive or specific to identify all malignant nodules. However, a combination of solid nodules, nodules with irregular contours, symptomatic nodules, and positive BRAF mutation has high predictive value for malignancy in patients with a cytologic diagnosis of AUS/FLUS.     

Role of lactate in the brain energy metabolism: revealed by Bioradiography

To elucidate the role of lactate in the brain, we used a novel method, 'Bioradiography', in which the dynamic process could be followed in living slices by use of positron-emitter-labeled compounds and imaging plates. We studied the incorporation of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) into rat brain slices incubated in oxygenated Krebs-Ringer solution. Under the glucose-free condition, [18F]FDG uptake rate in the cerebral cortex decreased with time and plateaued within 350 min but the addition of 5 mM lactate made the [18F]FDG uptake linear. When an inhibitor of the lactate transporter, 0.5 mM alpha-cyano-4-hydroxycinnamate (4-CIN) was applied to the glucose-free solution, the uptake rate decreased. Under the normal glucose condition, [18F]FDG uptake linearly increased for 6 h, but when 10 mM lactate was applied, the uptake rate decreased. In contrast, when 0.5 mM 4-CIN was applied to the normal glucose solution, [18F]FDG uptake rate increased. These results suggest that exogenous and endogenous lactate can substitute for glucose in the brain.     

顽固性癫（间）患者的PET、EEG和MRI对比研究

目的 :比较顽固性癫患者的正电子发射计算机断层扫描 (PET)、脑电图 (EEG)、磁共振成像 (MRI)结果 ,探讨脱氧葡萄糖 (18F FDG)PET对致灶进行定位的可行性和应用价值。方法 :10 2例顽固性癫患者 (男 6 4例 ,女 38例 ,平均年龄 2 2 1岁 )进行18F FDGPET脑显像 ,发作期显像 5例 ,发作间期显像 97例 ,全部病例均行EEG检查 ,4 8例作过MRI检查 ,分析比较PET、EEG和MRI定位致灶的有效性。结果 :PET发作期显像主要为局部高代谢 ,发作间期显像为 1个或多个低代谢灶 ,阳性检出率为92 4 % ,定侧定位率 5 2 9% ,PET对致灶的检出率和定侧定位率均明显高于EEG和MRI(P <0 0 1) ;EEG与PET检出的符合率为 4 1 2 % ,MRI与PET检出的符合率 4 1 7%。结论 :癫患者18F FDGPET脑显像是一种敏感而安全的定位顽固性癫致灶的有效方法 ,明显优于EEG和MRI,但PET所示异常低代谢区是否均为致灶尚存在质疑 ,联合EEG和MRI可提高灶检出阳性率及定位准确性。     

Utility of F-18 fluorodeoxyglucose pos?tron em?ss?on tomography/computed ?n carc?noma of unknown primary

Carcinoma of unknown primary (CUP) is a heterogeneous group of tumors with various clinical features causing diagnostic and therapeutic challenges. The aim of this study was to evaluate the ability of F-18 FDG PET/CT for localizing the primary tumor, disclosing additional metastases, and changing the treatment in patients with CUP. One hundred and twelve metastatic patients (female = 40, male = 72, median age = 60.5 years) in whom conventional diagnostic work-up failed to disclose the primary tumor were included in the study. F-18 FDG PET/CT imaging was performed in a standard protocol (patient supine, arms on patient’s side, vertex to thigh, 369.3 MBq (296-444 MBq) F-18 FDG, a 60-minute uptake period, 6-7 bed position). Histopathology was taken as the only reference standard. F-18 FDG PET/CT correctly detected primary tumor in 37 of 112 (33.03%) patients. The most common site of primary tumor detected by F-18 FDG PET/CT was lung (n = 18), which was followed by nasopharynx (n = 7), pancreas (n = 5), tonsil (n = 2), breast (n = 2), thyroid (n = 1), uterus (n = 1) and colon/rectum (n = 1). F-18 FDG PET/CT imaging disclosed additional previously undetected metastases in 32 (28.5%) and changed the treatment in 33 (29.4%) of 112 patients. There were false positive F-18 FDG PET/CT results in 21 (18.5%) patients. F-18 FDG PET/CT is able to disclose the primary tumor, disclose new metatases and change the treatment in about one third of patients with CUP.     

Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Predicting the Adverse Effects of Chimeric Antigen Receptor T Cell Therapy in Patients with Non-Hodgkin Lymphoma

CD19-targeting chimeric antigen receptor (CAR)-T cell therapy has shown great efficacy in patients with relapsed/refractory non-Hodgkin lymphoma (NHL) but has been associated with serious adverse effects, such as cytokine release syndrome (CRS). It has been speculated that NHL baseline disease burden might affect clinical outcome and CRS, but this has not been explored in detail in any previous study. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG), as measured by fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET-CT), are quantitative indicators of baseline tumor burden. Using FDG PET-CT, we calculated baseline and post-CAR-T cell therapy MTV and TLG in 19 patients with NHL. The median MTV was 72 cm³ (range, .02 to 1137.7 cm³), and the median TLG was 555.9 (range, .011 to 8990.3). After a median follow-up of 5 months (range, 1 to 12 months), the best overall response rate was 79.0%. The baseline MTV and TLG did not differ significantly between patients with response and those without response (P = .62 and .95, respectively). On Cox regression analysis, baseline MTV and TLG were not significantly associated with overall survival (P = .67 and .45, respectively). Patients with mild and moderate CRS (grade 0 to 2) had significantly lower MTV and TLG than those with severe CRS (grade 3 to 4) (P = .008 for MTV comparison, P = .011 for TLG comparison). Using FDG PET-CT, we also demonstrated that CAR-T cell therapy in patients with NHL was associated with pseudoprogression and local immune activation. Our data indicate that patients with higher baseline disease burden have more severe CRS, and that CAR-T cell therapy is associated with lymphoma pseudoprogression and local immune activation.     

Repeat thyroid nodule fine-needle aspiration in patients with initial benign cytologic results

Fine-needle aspiration (FNA) is the standard of care for the initial workup of thyroid nodules, but there is no consensus algorithm to manage patients with benign results. We examined performance characteristics of initial and repeat satisfactory FNAs for all 402 patients who underwent thyroid surgery during a recent 22-month period. Of these patients, 267 had at least 1 satisfactory FNA and 70 had 2 or more. After an initial benign FNA, 1 repeat FNA correctly identified an unsuspected malignancy in 2 of 70 patients and was indeterminate in 17; of these, 7 of 17 were identified as malignant in the final pathologic diagnosis. Overall, the use of 1 repeat FNA increased the sensitivity for malignancy from 81.7% to 90.4% and decreased the false-negative rate from 17.1% to 11.4%. With more than 1 repeat FNA, there was no improvement in performance characteristics. These data make a strong argument for 1 repeat FNA following an initial benign FNA diagnosis.     

Clinical characteristics and outcomes of clostridial bacteraemia in cancer patients

Clostridial bacteraemia is usually associated with substantial morbidity and mortality in cancer patients. However, clinical characteristics and risk factors for early mortality in this population are poorly described. We retrospectively studied cancer patients with clostridial bacteraemia treated between January 1996 and December 2011. We compared clinical manifestations between patients with solid tumour and haematological malignancy and assessed risk factors for 7-day mortality. In all, 164 cancer patients developed clostridial bacteraemia during the study period—85 (52%) with solid tumour and 79 (48%) with haematological malignancy. Common isolates were Clostridium perfringens (27%), Clostridium septicum (19%) and Clostridium tertium (14%). Solid tumour malignancy patients were more likely to have a focal gastrointestinal source for bacteraemia and were more likely to undergo subsequent surgery. Haematological malignancy patients were more often neutropenic and more often had no focal source of bacteraemia. Seven-day mortality was 20% (33/164) and did not vary based on malignancy type. The adjusted odds ratio of dying within 7 days of clostridial bacteraemia among patients with hypotension (40/164) was 7.2 (95% CI, 2.9–18.1) and in patients with acute haemolysis (7/164) was 10.5 (95% CI, 1.3–85.2). Clostridial species also impacted mortality; no patient with C. tertium bacteraemia died within 7 days. In conclusion, clinical manifestations of clostridial bacteraemia differed between patients with solid tumour and haematological malignancy, but 7-day mortality was similar. Patients with hypotension and haemolysis at time of bacteraemia were at increased risk for early death.     

Evaluation of Incidental Thyroid Nodules in Cancer Patients

Objective

Frequency of thyroid cancer in incidental thyroid nodules identified by imaging techniques in cancer patients is higher than that in the normal population. In the retrospective study, we have both investigated the incidence of thyroid cancer in incidentally identified nodules and compared the imaging techniques to determine whether there is any difference between them in detection of malign nodules.

Is pneumosinus dilatans an osteogenic disease that mimics the formation of a paranasal sinus?

Purpose

Pneumosinus dilatans is a disease that produces an abnormal expansion of a paranasal sinus cavity, which contains only air and is lined by normal mucosa, and whose bony walls are displaced outwardly to cause facial embossing or intracranial, orbital or ethmoidal encroachment. Objective was to evaluate the hypothesis that pneumosinus dilatans is primarily an osteogenic disease.

Methods

A detailed clinical history of three consecutive patients with pneumosinus dilatans was taken. Each patient also underwent computed tomography (CT), fluorine-deoxyglucose positron emission tomography-CT (FDG PET-CT), fluorine 18-labeled sodium fluoride PET-CT (NaF PET-CT), and bone pathology.

Results

The FDG PET-CT and pathology confirmed that the mucosa inside the pneumosinus dilatans was normal and devoid of inflammatory cell infiltrate. Significant uptake of ¹⁸F-NaF on PET-CT images correlated well with bone pathology, showing intense and diffuse bone remodeling. At a 1-year follow-up, following a frontotomy for case #1 and a middle antrostomy for case #2, there was a marked resolution of the patients’ clinical symptoms and deformities, new bone formation on the walls, stabilization of the new sinus shape and volume, and persistence of significant uptake of ¹⁸F-NaF.

Conclusions

Pneumosinus dilatans is a rare disease. Its diagnosis is based on CT scan images. This study has shown that ¹⁸F-NaF PET-CT and bone pathology are useful modalities for the positive diagnosis of difficult cases. Pneumosinus dilatans appears to be an osteogenic disease. Further research is needed to investigate a possible link between mechanisms involved in paranasal sinus formation and those involved in pneumosinus dilatans.     

Possible role of FDG-PET in the early prediction of therapy outcome in liver metastases of colorectal cancer

Nonresectable colorectal cancer metastases in the liver respond to chemotherapy in 20-25% only. Early identification of nonresponders might allow the use of other regimens. In a limited feasibility study, it should be determined whether (a) a single high-dose chemotherapy application has an early effect on glucose-utilization, detectable and quantitatable by noninvasive positron emission tomography using [18F]-Fluoro-deoxyglucose (FDG-PET) and (b) assess its value as a predictor of the final therapeutic outcome. A total of 10 patients with documented nonresectable liver metastases of a colorectal cancer were studied by FDG-PET, prior and 72 h after a single infusion of 5-Fluorouracil and Folinic acid (5-FU/FA). Glucose utilization was quantitated by determination of standard-uptake values and correlated with final therapy outcome following completion of the anticipated therapy cycle. Patients were followed up for at least 6 months. All metastases responding to therapy (n = 6) exerted a statistically significant decrease of FDG uptake (-22+/-10%), metastases (n = 2) showing a short-term effect (duration of tumor reduction <3 months) had a slightly diminished, and progressing metastases (n = 3) an enhanced FDG uptake (13+/-17%). Our preliminary data indicate that acute changes of glucose utilization-as detected by FDG-PET-following a single application of chemotherapy, seems to be indicative for the final therapeutic outcome, at least in liver metastases of colorectal cancer.     

Case Report: Adrenal Oncocytoma Associated with Markedly Increased FDG Uptake and Immunohistochemically Positive for GLUT1

Usually, benign tumors are not associated with an increased F-18 fluorodeoxyglucose (F-18 FDG) uptake on positron emission tomography (PET), although some exceptions have been reported in adrenal neoplasms. We present a rare case of adrenocortical oncocytoma associated with markedly increased FDG uptake, demonstrating a maximum standardized uptake value of 46.8. Histological examination demonstrated diffuse proliferation of tumor cells with eosinophilic and granular cytoplasm that were diffusely immunopositive for mitochondria and glucose transport protein 1, with focal and weak immunopositivity for 3β-hydroxysteroid dehydrogenase. Ultrastructural examination also revealed abundant mitochondria in the tumor cells. The tumor was diagnosed as adrenocortical oncocytoma and was considered benign according to Lin-Weiss-Bisceglia criteria. Diagnosis of adrenocortical oncocytoma can pose difficulties during both preoperative radiological and postoperative histopathological investigations.     

The role of F-18FDG PET in thyroid cancer

Hypofunctioning nodules on scintiscan using Tc-99m Pertechnetate or I-123 have a higher probability of malignancy compared to eu- or hyperfunctioning nodules. However, in the preoperative assessment of thyroid nodules, ultrasonography and ultrasonography guided fine needle aspiration biopsy play the most important role, especially for papillary thyroid cancer. The problem of differentiating follicular adenoma from highly differentiated follicular carcinoma however remains. Also the additional use of a multi tracer imaging strategy (Tl-201/Tc-99m subtraction scan, Tc-99m Sestamibi, Tc-99m Tetrofosmin dual phase scintigraphy) has not solved this problem. Although it is unlikely, the question whether FDG PET is able to give a better differentiation between benign and malignant tumours in the preoperative assessment of thyroid nodules is not answered up to now. In contrast to preoperative diagnostics, FDG PET is of great value in the postoperative follow up of differentiated thyroid cancer. In case of elevated serum thyroglobulin but negative I-131 WBS FDG PET is the method of choice to detect I-131 negative recurrences and metastases. FDG uptake in metastases from differentiated thyroid cancer is correlated to low differentiation and maybe bad prognosis. There is also evidence that FDG PET may have a role in the follow up of anaplastic and especially in medullary thyroid cancer in the future.     

Clinical profile and outcome of non-HIV-infected patients with cryptococcal meningitis and malignancy

BackgroundCryptococcal meningitis (CM) can coexist with malignancy in patients not infected by human immunodeficiency virus (HIV). The purpose of this study was to evaluate the clinical characteristics and therapeutic outcomes of non-HIV-infected patients with CM with malignancy.MethodsThe study cohort comprised 320 patients diagnosed with CM from January 2013 to May 2019. Malignancy was diagnosed based on the medical history, imaging findings, and pathological findings. One-hundred-and-four patients also underwent positron emission computed tomography (PET-CT) examination to enable the early detection of possible malignancies. The demographics, clinical characteristics, and outcomes were analyzed.ResultsTwelve patients with CM with malignancies were found. Seven were patients with CM who had a history of malignancies (CM in malignancy; CIM), while five patients had malignancies detected after being diagnosed with CM (malignancy in CM; MIC). The patients with CM with malignancies, especially MIC, were older than those without malignancies. The outcome was similar for patients with CIM and patients with CM without malignancy, but was extremely poor for patients with MIC. PET-CT examination suggested malignancy in five of 104 patients, with malignancy finally confirmed in four of five patients.ConclusionsCompared with the general population, the rate of solid malignancies was increased in patients with CM, especially older adults. The presence of malignancies and timing of discovery were closely related to the outcome of patients with CM. Thus, it is necessary to screen for malignancies in older adults with CM. PET-CT might be useful for early malignancy screening of patients with CM.     

PET-CT 与 MRI 诊断中国人鼻咽癌转移的 Meta 分析简

目的通过Meta分析比较正电子计算机断层摄影术-计算机X线体层摄影术（PET—CT）与MRI对中国人鼻咽癌转移的诊断价值。方法用计算机检索万方数据库、中国学术期刊网全文数据库（CNKI）和维普数据库从1989年1月至2013年5月收录的PET-CT与MRI诊断中国人鼻咽癌转移的临床文献．对纳入文献采用Meta—Disc软件进行Meta分析。结果最终纳人文献5篇,共636例患者。Meta分析结果显示。PET—CT诊断鼻咽癌转移95％可信区间（CI）的灵敏度（SEN）、特异度（SPE）分别为35％（33％。37％）、94％（91％～96％）,受试者工作特征（SROC）曲线下面积（AUC）为0．7247．标准误（SE）（AUC）为0．2399;而MRI诊断鼻咽癌转移95％CI的SEN、SPE分别为35％（33％～37％）、84％（80％～87％）．SROCAUC为0．7654,SE（AUC）为0．1154。以上结果表明．与MRI相比,PET-CT在中国人鼻咽癌转移诊断中具有较低的误诊率．但诊断价值稍低。结论根据现有的临床诊断文献．PET—CT和MRI均是诊断中国人鼻咽癌转移的有效技术手段。在误诊率方面．PET—CT优于MRI;但诊断价值稍低。因此,两者紧密结合才能使鼻咽癌转移的检出率明显增高。     

The Value of Negative Diagnosis in Thyroid Fine-Needle Aspiration: a Retrospective Study with Histologic Follow-Up

The Bethesda System for reporting thyroid cytopathology (BSRTC) predicts an incidence of malignancy of less than 5% in thyroid nodules with a benign diagnosis on fine-needle aspiration (FNA). However, recent series have suggested that the true rate of malignancy might be significantly higher in this category of patients. We reviewed our experience by performing a retrospective analysis of patients with benign thyroid FNA results who underwent thyroidectomy between 2008 and 2013 at a large academic center. Information including demographics, ultrasound features, FNA diagnosis, and surgical follow-up information were recorded. Slides were reviewed on cytology-histology discrepant cases, and it was determined whether the discrepancy was due to sampling or interpretation error. A total of 802 FNA cases with a benign diagnosis and surgical follow-up were identified. FNA diagnoses included 738 cases of benign goiter and 64 cases of lymphocytic thyroiditis. On subsequent surgical resection, 144 cases were found to be neoplastic, including 117 malignant cases. False negative, defined as interpretation error and inadequate biopsy of the nodule harboring malignancy, was 6%. When cases of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were excluded from the analysis, false-negative rate was 5%. When microPTC cases were excluded, false-negative rate was 3% and was slightly less than 3% when both microPTC and NIFTP cases were excluded from the analysis. Retrospective review of neoplastic cases showed that 57% were due to sampling error and 43% were due to interpretation error. Interpretation error was more likely to occur in follicular patterned neoplasms (75%), while sampling error was more common in non-follicular variants of papillary thyroid carcinoma (non-FVPTC) (61%). With the exclusion of microPTC, interpretation errors were still more likely to occur in follicular neoplasms (79%) but there was no significant difference in sampling error between non-FVPTC (37%) and follicular patterned neoplasms (42%). Tumor size was larger in cases with interpretation error (mean = 2.3 cm) compared to cases with sampling error (mean = 1.4 cm). This study shows that the false-negative rate of thyroid FNA at our institution is not significantly above the rate suggested by the BSRTC. Interpretation errors were more likely to occur in follicular patterned neoplasms, while non-FVPTC was more frequently found in false negative cases due to inadequate sampling.     

Understanding of cerebral energy metabolism by dynamic living brain slice imaging system with [18F]FDG

Recently, lactate has been receiving great attention as an energy substrate in the brain. In this study, the role of lactate was evaluated by "bioradiography" system with 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG), which is a positron emitting radiotracer for glucose uptake quantification. "Bioradiography" is the dynamic living tissue slice imaging system for positron-emitter labeled compounds. We investigated the brain energy metabolism under resting state and neural activated conditions induced by KCl addition. The monocarboxylate transporter inhibitor, alpha-cyano-4-hydroxycinnamate (4-CIN), had no effect on [(18)F]FDG uptake rate in rat brain slices before KCl addition. On the other hand, addition of 4-CIN induced larger [(18)F]FDG uptake rates under the activated condition in comparison with the control condition. Because neurons cannot utilize lactate under the 4-CIN loaded conditions, this indicates that activated neurons consume lactate as an energy substrate. The lactate concentration in the incubation medium was increased with KCl treatment in both groups and the extent was slightly greater in 4-CIN group. These results suggested that: (1) the brain mainly uses glucose, not lactate, as an energy substrate in resting state; (2) when neuron is stimulated, excess amounts of lactate might be produced in astrocytes and the lactate is mobilized as an energy substrate.     

Excision biopsy findings of patients with breast needle core biopsies reported as suspicious of malignancy (B4) or lesion of uncertain malignant potential (B3)

AIMS: The UK National Health Service Breast Screening Programme has proposed five categories for reporting breast needle core biopsies. The majority of cores are reported as benign (B1), normal (B2) or malignant (B5). The predictive value of the two borderline categories suspicious of malignancy (B4) and lesion of uncertain malignant potential (B3) was studied. METHODS AND RESULTS: Over a 2-year period a total of 3822 breast needle core biopsies were performed, with 2997 from symptomatic patients and 825 from women undergoing mammographic screening, including 43 B4 reports (40 patients) and 120 B3 reports (116 lesions in 115 patients). The frequencies of B4 (2.5% versus 0.7%) and B3 cores (7.3% versus 2.0%) were both higher in screening than in symptomatic patients. B4 was most commonly used for small fragments of atypical cells separate from the main core or focal atypical intraductal proliferations. The criteria for calling a core B3 were: atypical intraductal epithelial proliferations (including foci that in excision specimens would be classified as atypical ductal hyperplasia), lobular neoplasia, radial scar, papillary lesion, fibroepithelial lesion with cellular stroma and spindle cell proliferations. Excision biopsies were performed in 39 patients with B4 core and 96 with B3 core. Invasive carcinoma or ductal carcinoma in situ was seen in 33 of the patients with B4 (85%) and in 29 of those with B3 cores (25%). Some categories of B3 core were associated with a higher rate of malignancy (40% for atypical intraductal epithelial proliferations and 46% for lobular neoplasia). CONCLUSIONS: The positive predictive value for carcinoma is high following a B4 core (86%). The lesion should be excised, but definitive cancer treatment is not appropriate. In some cases a definite diagnosis of malignancy can be made on repeat core. The B3 group is more heterogeneous and has a lower rate of malignancy on further biopsy (25%). The majority of B3 lesions require excision. All these patients should be discussed at multidisciplinary meetings.     

Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections

Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [¹⁸F]FDG ([¹⁸F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [¹⁸F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6–75 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [¹⁸F]FDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [¹⁸F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [¹⁸F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [¹⁸F]FDG-PET was performed to assess the evolution of the disease. [¹⁸F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [¹⁸F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.     

Value of Ultrasound and Cytological Classification System to Predict the Malignancy of Thyroid Nodules with Indeterminate Cytology

Although fine-needle aspiration cytology is considered the gold standard for evaluating thyroid nodules, in about 10–30% of the cases, cytology is indeterminate. This study aimed to determine the value of cytological classification system and ultrasound (US) to predict malignancy in indeterminate thyroid nodule. This retrospective analysis enrolled 80 patients surgically treated at a single center, 75% (60) with benign vs. 25% (20) with malignant lesions at final histology. The clinical, scintigraphic, sonographic, and cytological classification (Bethesda) variables were analyzed in these selected cases of indeterminate cytology, and a prediction model was designed after the multivariate analysis. There was a 25% prevalence of malignancy (20/80). There were no differences in gender, serum thyroid-stimulating hormone and FT4 levels, thyroid auto-antibodies, thyroid dysfunction, and scintigraphic results between benign and malignant nodule groups. The border irregularity in sonographic study was at increased risk for malignancy. The cytological analysis based on Bethesda System (category IV) was an independent predictor for malignancy in indeterminate thyroid nodules. After the multivariate analysis, the model obtained showed border irregularity and Bethesda System category IV as predictive factors of malignancy in indeterminate thyroid nodules, featuring 76.9% of accuracy. This study confirmed a significant increase of risk for malignancy in thyroid nodules with indeterminate cytology showing Bethesda System category IV and suspicious features at US. These findings enhance our current limited predictive armamentarium and can be used to guide surgical decision making.