Compartment Lymph Node Research Articles

Evaluation of a panel of antibodies for the immunohistochemical identification of immune cells in paraffin-embedded lymphoid tissues of new- and old-world camelids

Different species of camelids play an important role in the epidemiology of various emerging infectious diseases such as Middle East respiratory syndrome. For precise investigations of the immunopathogenesis in these host species, appropriate immunohistochemical markers are highly needed in order to phenotype distinct immune cells populations in camelids. So far, specific immunohistochemical markers for camelid immune cells are rarely commercially available, and cross-reactivity studies are restricted to the use of frozen dromedary tissues. To bridge this gap, 14 commercially available primary antibodies were tested for their suitability to demonstrate immune cell populations on formalin fixed paraffin-embedded (FFPE) tissue sections of dromedaries, Bactrian camels, llamas, and alpacas in the present study. Out of these, 9 antibodies directed against CD3, CD20, CD79α, HLA-DR, Iba-1, myeloid/histiocyte antigen, CD204, CD208, and CD68 antigen exhibited distinct immunoreaction patterns to certain camelid immune cell subsets. The distribution of these antigens was comparatively evaluated in different anatomical compartments of thymus, spleen, mesenteric, and tracheobronchial lymph nodes. The presented results will provide a basis for further investigations in camelids, especially with respect to the role of the immune response in certain infectious diseases, which harbor a considerable risk to spill over to other species.

Papillary Thyroid Carcinoma: Analysis of the Central Compartment's Lymph Nodes Metastases.

Papillary thyroid carcinoma is typical by regional lymph nodes metastases. Therefore we decided to analyse associated risk factors. In this retrospective study we focused on the incidence of metastatic involvement of the central compartment's lymph nodes correlated with age, size of the primary tumour, infiltration of thyroid gland capsule, positive lymphangioinvasion in order to assess risk factors. We analysed group of 156 patients with papillary carcinoma, who have undergone total thyroidectomy and bilateral elective central compartment neck dissection. We evaluated the occurrence of metastases, size, infiltration and lymphangioinvasion based on definitive histology of the whole group and separately for subgroups of patients under and over 45 years. We found metastatic involvement in 88 (56.4%) patients. When comparing the subgroups of patients under (73 patients) and over 45 years (83 patients), we found metastases in 56 vs. 32 (76.7% vs. 38.6%) patients. In the subgroup of younger patients we found significant higher incidence of metastases compared with the group of over 45 years, P < 0.001 (P = 0.000027). We found significant higher incidence of metastases in patients with positive capsule infiltration in the whole group, P < 0.001 (P = 0.00049); in the subgroup of under 45 years, P < 0.001 (P = 0.00091) and in patients with positive lymphangioinvasion in the whole group, P < 0.01 (P = 0.00177); in the subgroup of over 45 years, P < 0.001 (P = 0.0002). In patients with metastases we found tumour size ≥1cm more frequently in all groups. We recorded higher incidence of regional metastases in patients under 45 years, positive capsule infiltration, lymphangioinvasion. Age under 45 years itself does not correlate with less aggressive disease, to the contrary some of other analysed risk factors correlate with more aggressive disease.

95A. Local recurrence in the lateral lymph node compartment in rectal cancer: Improved outcomes with induction chemotherapy combined with multimodality treatment

95A. Local recurrence in the lateral lymph node compartment in rectal cancer: Improved outcomes with induction chemotherapy combined with multimodality treatment

Local Recurrence in the Lateral Lymph Node Compartment: Improved Outcomes with Induction Chemotherapy Combined with Multimodality Treatment

Lateral nodal disease is of major importance in the treatment of rectal cancer in the East, but a mostly neglected entity in the West. In this article, the treatment of recurrences in the lateral compartment (latLRs) in a national tertiary referral center is evaluated. Of 214 patients with locally recurrent rectal cancer who underwent multimodality treatment in the Catharina Hospital in the last 10years, a total of 51 patients with latLR were selected (the latLR region was classified as upper, middle, or lower). Thirteen (25%) of these patients underwent induction chemotherapy (ICT) prior to chemo(re)irradiation. LatLRs occurred mainly after low and N+ primary tumors. Seven (14%) patients had a complete response (pCR) and 28 (55%) underwent an R0 resection. Patients with a lower latLR had the highest chance of undergoing an abdominoperineal resection and resection of anterior organs. ICT resulted in a 31% pCR rate compared with 8% without ICT (p=0.039). Patients who received ICT had an 85% R0 resection rate, while this was 45% in patients who did not receive ICT (p=0.013). The 5-year local re-recurrence (LRR) rate was 64.3%, and overall survival (OS) was 34.2%; the only factor improving these was an R0 resection. Five-year survival after multivariate analyses was 10.3% after an R+ resection compared with 66.8% after an R0 resection (p=0.011). LatLRs impose a major surgical challenge and result in high LRR and low OS. More R0 resections can possibly be achieved with ICT, which is the only factor that can improve LRR and OS.

¹⁸F-FDG PET/CT-Guided Clinical Management of the Rare Aggressive "Columnar-Cell" Variant of Papillary Thyroid Cancer.

A 61-year-old man underwent 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) staging for biopsy-proven thyroid carcinoma with right neck nodal metastases (Fig. 1A). Total thyroidectomy with central and right neck lymph node dissection was performed. Final histological diagnosis was columnar-cell (CC) variant of papillary thyroid cancer (PTC) and multiple nodal metastases (Fig. 1E). One month later, adjuvant radioiodine treatment (5,550 MBq) was performed, and the post-therapeutic whole-body scan showed only minimal uptake in the thyroid bed, consistent with remnant thyroid tissue (Fig 1B). At patient discharge, serum thyroglobulin was 137 ng/dL. Fig. 1 (A) Preoperative 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) scan showing the primary tumor in the right thyroid lobe and gross metastatic right neck lymph nodes. (B) Post-operative 131 whole body scan showing ... Three months later, a newly growing lymphadenopathy in the anterior median neck and hard subcutaneous nodules in the left cervical region were detected by a physical examination and ultrasound. They were confirmed as thyroid cancer metastases by fine-needle aspiration biopsy. For restaging purposes, the patient underwent a second 18F-FDG-PET/CT examination, which identified a suspicious lymphadenopathy in the right supraclavicular fossa (Fig. 1C, arrow) in addition to the known lesions. Serum thyroglobulin was 65 ng/dL at the time. The patient underwent revision surgery of the central and right neck lymph node compartments, in addition to left cervical nodal dissection and surgical removal of the subcutaneous nodules. Histology confirmed metastases of CC PTC in the left cervical soft-tissues (Fig. 1F) and in seven of the total 22 nodes that were removed. Based on the rapid and extended recurrence and the tumor dedifferentiation evidenced by the PET/CT findings, external-beam radiation therapy was recommended as an adjuvant treatment. A total of 44 Gy was delivered to the neck by intensity-modulated radiation therapy. Six months later, serum thyroglobulin dropped to 0.1 ng/dL and 1 year later, a follow-up 18F-FDG-PET/CT scan showed no signs of disease recurrence (Fig. 1D). CC is a rare histological subtype of PTC, usually associated with more aggressive behavior and a worse overall outcome than the classical variant [1]. In such instances, strict postoperative monitoring is recommended as the early detection and treatment of recurrence may significantly improve survival [2]. Several studies suggested that 18F-FDG-PET/CT may be a potentially valuable technique in the staging and surveillance of patients with aggressive subtypes of differentiated thyroid cancer such as the CC variant, although there is no definite consensus regarding its indications in routine clinical practice [3]. This is the first reported case of CC PTC evaluated by 18F-FDG-PET/CT, which was a useful tool in all phases of management for this patient.

CD180 overexpression in follicular lymphoma is restricted to the lymph node compartment.

Altered Toll-like receptor (TLR) expression levels and/or mutations in its signaling pathway (such as MyD88 mutation) contribute to the pathogenesis of lymphoproliferative disorders (LPD). CD180 is an orphan member of the TLR family that modulates the signaling of several TLRs, but only limited studies have evaluated its expression by flow cytometry (FCM) in LPD. Using a multiparameter FCM approach, we have assessed CD180 mean fluorescence intensity (MFI) in lymph nodes (LNs) and peripheral blood (PB) samples obtained from patients with follicular lymphoma (FL; LN/PB, n = 44/n = 15), chronic lymphocytic leukemia (CLL, n = 26/n = 21), mantle cell lymphoma (MCL, n = 13/n = 17), and marginal zone lymphoma (MZL, n = 16/n = 12). Specimens from non-tumoral PB and LN (n = 8/n = 12) were used as controls. In the LN specimens, FL and control B-cells showed similar CD180 expression (MFI = 1,049 vs. 1,381, P > 0.05; Mann-Whitney U-test). This level was markedly lower in the other LPDs, MCL (MFI = 396, P < 0.05), or CLL (MFI = 502 P < 0.05), and similar to MZL (MFI = 858, P > 0.05). However, the CD180 expression of FL B-cells assessed in PB was dim and/or negative, in the same range as MCL and CLL (FL MFI = 453, MCL MFI = 305, CLL MFI = 420, P > 0.05) but lower than in MZL (MFI = 895, P < 0.05). Therefore, these results suggest a modulation of CD180 expression by neoplastic FL B-cells based on the anatomical compartment. These FCM data confirm the usefulness of CD180 in the accurate diagnosis of LPDs and emphasize the need to interpret this marker according to the origin of the sample. © 2015 Clinical Cytometry Society.

In-Vivo Labelling Studies in Patients with Chronic Lymphocytic Leukemia Studies Demonstrate the Existence of Apparently Distinct Subpopulations That Differ in Phenotype and Proliferative Capacity

It is now generally believed that proliferation of the neoplastic clone in chronic lymphocytic leukemia (CLL) takes place in lymphoid tissues where interactions involving the B-cell receptor (BCR) and other microenvironmental elements take place. Previous studies using in-vivo labelling with deuterated water have shown that recently proliferated emigrants from lymphoid tissues express low levels of the chemokine receptor CXCR4 and high levels of CD5 (CXCR4loCD5hi). It has been proposed that, following entry into the peripheral blood (PB), these cells become quiescent, re-express CXCR4 and downregulate CD5 allowing re-entry into tissues and further rounds of proliferation. In the present study we used in-vivo labelling with deuterated glucose (6,6-2H2-glucose, D2G) to investigate the proliferation and release of CLL cells into PB. In contrast to deuterated water, this technique allows pulse labelling of a distinct cohort of cells, which can then be tracked over time in-vivo.Labelling studies were performed in 10 patients with previously untreated, non-progressive CLL. Patients underwent 10 hours of labelling with oral 2DG, after which peripheral blood and lymph node compartments were serially sampled. DNA Deuterium enrichment was measured in the entire CLL population and in flow-sorted subsets defined by CXCR4/CD5 and surface IgM (sIgM) expression.Maximum release of labelled cells into PB occurred after a median of 14 days (4-56 days). The disappearance rate was very slow, with labelled cells detectable after 56 days in half of the subjects. In one case we were able to track labelled cells in both lymph node (LN) and PB and demonstrated an increase in the fraction of labelled cells in the LN between days 7 and 28, consistent with re-entry into this compartment.Subpopulations of PB CLL cells, defined by CXCR4 and CD5 expression were studied over time to investigate the dynamic nature of these molecules in circulating cells. As previously reported, maximum rapid incorporation of deuterium was observed in the CXCR4loCD5hi fraction, equivalent to 1.15 ± 0.04 %/d fractional synthesis at 7 days. Conversely, CXCR4hiCD5lo cells remained largely unlabelled throughout the 8-week study, reaching a maximum of only 0.01 ± 0.003 %/d, suggesting that they represent a non-proliferating population, not derived from the CXCR4loCD5hi subset. In contrast, CXCR4/CD5 intermediate cells exhibited delayed and intermediate labelling, peaking at 0.1 ± 0.02 %/d at 28 days. This sequential labelling pattern suggests that they derive from the CXCR4loCD5hi subset.Since both CXCR4 and CD5 expression are modulated by BCR signalling, we went on to sort cells according to sIgM expression and found maximum labelling in the sIgM high subset with little or no deuterium incorporation in the sIgM low fraction at any time. Again, the sIgM intermediate subset showed delayed labelling, suggesting that they are derived from sIgM-high cells.These observations provide further evidence for clonal heterogeneity in CLL and suggest the existence of distinct but interdependent subpopulations. Recently-divided cells are CXCR4loCD5hi, but appear to transition to an intermediate phenotype by down-regulation of CD5 and sIgM and upregulation of CXCR4 over the ensuing weeks, but do not appear to transition to CXCR4hiCD5lo cells over the time-course of the experiment. Our findings have clinical relevance, since these functionally distinct subsets might also differ in their responsiveness to therapeutic agents, such as drugs that block BCR signalling. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Risk factors and indication for dissection of right paraesophageal lymph node metastasis in papillary thyroid carcinoma

BackgroundRight paraesophageal lymph nodes (RPELNs) are located behind right recurrent laryngeal nerve which often ignored in central compartment lymph nodes (LNs) dissection of papillary thyroid carcinoma (PTC) patients. The aim of this study was to identify the risk factors for RPELN metastasis and indications for RPELN dissection. MethodsMedical record of 246 consecutive PTC patients (194 female, 52 male), who underwent total thyroidectomy (244 patients) or right lobectomy (2 patients) with central compartment LN dissection (13 ipsilateral and 233 bilateral), were reviewed. The RPELNs were kept separately during the operation. The clinical pathology data was collected and analyzed. ResultsRPELN metastasis was confirmed in 33 patients (13.4%) and were discovered in 18.5% (31/168) of right lesion, 34.4% (31/90) of right central group LN (rCLN) metastasis, 33.3% (18/54) of lateral compartment LN (LLN) metastasis, 25.7% (9/35) of local recurrent patients respectively. The ultrasound suspected metastatic LNs, tumor diameter, tumor number, tumor location, and numbers of metastatic Delphian LNs, central group LNs (CLNs), rCLNs, and LLNs between patients with and without RPELN metastasis showed significant differences in univariate analysis (P < 0.05). In multivariate analysis, number of metastatic rCLNs (1–2: OR 13.6, 95% CI, 2.7–67.5; ≧3: OR39.4, 95% CI, 7.7–200.9), right side tumor (OR 6.4, 95% CI, 1.1–35.6), and three or more metastatic LLNs (OR 3.5, 95% CI, 1.2–10.2) were independent risk factors for RPELN metastasis. ConclusionsPTC patients with right lobe lesions, especially with potential rCLN metastasis, are at considerable risk of RPELN metastasis. RPELN dissection should be considered in these patients.

Impact of Toxoplasma gondii on Dendritic Cell Subset Function in the Intestinal Mucosa.

The function of mucosal dendritic cell (DC) subsets in immunity and inflammation is not well understood. In this study, we define four DC subsets present within the lamina propria and mesenteric lymph node compartments based on expression of CD103 and CD11b. Using IL-12p40 YFP (Yet40) reporter mice, we show that CD103(+)CD11b(-) mucosal DCs are primary in vivo sources of IL-12p40; we also identified CD103(-)CD11b(-) mucosal DCs as a novel population producing this cytokine. Infection was preferentially found in CD11b(+) DCs that were negative for CD103. Lamina propria DCs containing parasites were negative for IL-12p40. Instead, production of the cytokine was strictly a property of noninfected cells. We also show that vitamin A metabolism, as measured by ALDH activity, was preferentially found in CD103(+)CD11b(+) DC and was strongly downregulated in all mucosal DC subsets during infection. Finally, overall apoptosis of lamina propria DC subsets was increased during infection. Combined, these results highlight the ability of intestinal Toxoplasma infection to alter mucosal DC activity at both the whole population level and at the level of individual subsets.

Immature myeloid cells and tolerogenic cytokine profile in lung adenocarcinoma metastatic lymph nodes assessed by endobronchial ultrasound.

In lung cancer, the immune cell compartment of tumor-draining lymph nodes (TDLNs) dictate the response against tumors. This response is predominantly triggered by myeloid antigen-presenting cells (mAPCs) that capture antigens and, if matured, prime anti-tumor-specific T cell populations. However, the clinical role of mAPCs infiltrated in TDLN from lung cancer patients is poorly understood. The purpose of this study was to study mAPCs in TDLN from lung adenocarcinoma patients, in comparison to individuals with non-malignant diseases, using minimally invasive sampling methods. Mediastinal lymph nodes were assessed by endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA). mAPCs were characterized by flow cytometry and cytokine expression by quantitative polymerase chain reaction. The association with tumor burden, overall survival, and response to treatment was assessed. TDLN from lung adenocarcinoma patients (n = 24) showed a reduced immune cell compartment, but a higher level of infiltrating mAPCs, when compared with control lymph nodes (n = 17). A decreased expression of co-stimulatory molecules CD80/CD86 by TDLN and blood mAPC was observed. TDLN showed lower levels of TNF-α and IL-12 and increased levels of immunosuppressive cytokines TGF-β and IL-10. The IL-12 expression was inversely correlated with the percentage of infiltrated tumor cells, while IL-10 was directly correlated. Patients with lower expression of IL-12 in TDLN or lower expression of CD80/86 in blood mAPCs had worse overall survival and response to therapy. mAPCs of lung adenocarcinoma patients express less co-stimulatory molecules, and within TDLN, the cytokine profile is biased towards a tolerance-inducing phenotype. Patients with enhanced immune parameters have better survival and response to treatment. EBUS-TBNA allows the collection of viable specimens from TDLN that may provide further insight on relevant immunological mechanisms.

Surgery for Lymph Node Metastases of Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells, and can commonly spread to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the only effective option for curative therapy, reduction in tumor burden or effective palliation. In patients undergoing preventative operations for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is above 40 pg/ml. Systematic removal of at-risk or involved lymph node compartments should be performed in all patients with palpable primary tumors and recurrent disease, and a ‘berry-picking’ approach should be avoided.

Cervical lymph node metastasis in medullary thyroid carcinoma

To study the patterns of cervical lymph node metastasis of medullary thyroid carcinoma. Ninety-one patients with medullary thyroid carcinoma first treated between January 1999 and October 2014 were analyzed retrospectively. Of 91 patients, 39 cases presented with clinical negative node (cN0) and 52 cases with clinical positive node (cN+). Central compartment dissection was performed in all cases. Lateral neck dissection was performed in 52 cN+ cases (71 sides). All neck dissection specimens were obtained and analyzed for lymph node (LN) involvement with respect to neck levels. The distribution of LN with metastasis was studied in cN+ patients and the following factors were used to study the predictive value of central compartment LN metastasis: sex, age, family history, tumor size, bilateral tumor, multifocality of the tumor, extracapsular spread, and remote metastasis. Univariate analysis with the χ(2) test was used to analyze the statistical correlation between central compartment LN metastasis and other clinical factors. Multiple logistic regression analysis was used to identify the factors related to central compartment metastasis. Neck and bilateral neck metastasis rates were 73.6%, 19.8% respectively. Metastasis rates in central compartment and superior mediastinal region were 68.1% and 27.5% respectively. The central compartment metastasis rate was 33.3% in cN0 patients and 94.2% in cN+ patients. The superior mediastinal metastasis rate was 2.6% in cN0 patients and 46.2% in cN+ patients. Extracapsular spread was an independent predictive factor for central compartment metastasis (χ(2)=15.592, P=0.000, OR=12.876). The incidences of LN metastases at level II, III, IV, V were 62.9%,84.5%,83.1%,50.0% in cN+ patient, respectively. Multi-sites were involved. The possibility of lateral neck metastasis was higher when preoperative value of calcitonin was higher than 300 ng/L (66.7% vs 28.6%, χ(2)=5.771, P=0.016). Cervical lymph node metastasis of medullary thyroid carcinoma is higher. Central compartment dissection is necessary in cN0 patients with extracapsular spread. Neck dissection from level II to level VII was necessary in cN+ patients. Preoperative value of calcitonin maybe can predict the lateral neck metastasis incidence.

Role of carbon nanoparticles in patients with thyroid carcinoma undergoing total thyroidectomy plus bilateral central neck dissection

To evaluate the role of carbon nanoparticles for dissecting lymph nodes and preserving parathyroid glands in patients with thyroid carcinoma undergoing total thyroidectomy plus bilateral central neck dissection. A total of 86 patients with thyroid carcinoma undergoing primarily total thyroidectomy plus bilateral central neck dissection were randomly divided into trial and control groups. Carbon nanoparticles were injected into thyroid gland of trial group. Total lymph node, metastasis lymph node, black stained lymph node and black stained metastasis lymph node of trial group were counted in central compartment dissection specimens. And total lymph node and metastasis lymph node of control group were counted in central compartment dissection specimens. Parathyroid glands in central neck dissection specimens were counted in two groups. For two groups, serum total calcium and parathyroid hormone were measured pre-operation and 1 day, 3 days, 5 days, 1 month, 3 months and 6 months post-operation. In trial group, the average counts of (10.19 ± 4.27) lymph nodes and (8.44 ± 4.31) black stained lymph nodes were more than those in control group at (6.26 ± 2.98) lymph nodes (all P < 0.01). Parathyroid gland was found in trial group (n = 7) and control group (n = 11). And the difference had no statistical significance (χ(2) = 1.124, P = 0.289). The preoperative serum levels of calcium and parathyroid hormone decreased within 6 months postoperatively in both groups (all P < 0.01). Without extracapsular invasion, serum levels of calcium and parathyroid hormone were higher in trial group than those in control group at 5 days, 1 month and 3 months post-operation (all P < 0.05). In an event of lymph node metastasis, serum levels of calcium (t = 3.446, P = 0.001) and parathyroid hormone (t = 2.441, P = 0.017) in trial group were higher than those in control group at 1 month post-operation. When there was extracapsular invasion or no lymph node metastasis, the serum levels of calcium and parathyroid hormone had no inter-group statistical differences within 6 months post-operation (all P > 0.05). When tumor size was less than or equal to 4 cm, the level of parathyroid hormone was higher in trial group than that in control group at 1 month post-operation (t = 2.703, P = 0.009). But no inter-group statistical differences existed within 6 months post-operation (all P > 0.05) when tumor size surpassed 4 cm. Regardless of tumor size, the serum levels of calcium in trial group were higher than those in control group at 1 month post-operation (all P < 0.01). For thyroid carcinoma patients, total thyroidectomy plus bilateral central neck dissection increases the incidence of hypoparathyroidism. Lymph nodes of central compartment may be tagged by carbon nanoparticles so as to boost the detection rate of lymph node. In events of lymph node metastasis or no extracapsular invasion, carbon nanoparticles can adequately protect parathyroid functions.

P3 Peripheral tolerance in regional lymph nodes is associated with parameters of malignancy in oral squamous cell carcinomas

Background The peripheral immune tolerance might be a prerequisite for the progression of cancer and can help explaining the formation of lymph node metastases of solid malignancies. In this process macrophages are involved in mediating an immune tolerance towards tumor antigens. Tumor-tolerance mediating M2-macrophages might contribute to the formation of peripheral tolerance in oral squamous cell carcinomas (oscc). The phylogenetically highly conserved glycoprotein Galectin-3 (Gal-3) is involved in the regulation of macrophage polarization (M1/M2). The aim of this study is the comparing immunohistochemical analysis of Gal-3 expression and macrophage polarization in tumor free lymph nodes and lymph node metastases of primary oscc. Material and methods Metastatic- and non-metastatic lymph node samples obtained during lymph node surgery of oral squamous cell carcinomas ( n = 30), were investigated by immunohistochemistry. Automated staining with an LSAB-kit was used to detect CD68, CD11c, CD163, MRC1 and Gal-3 positive cells. Complete digitalization of all samples using “whole slide imaging” and quantitatively assessment of the number of stained cells per area was performed. The expression of markers in the different lymph node compartments was considered separately. The study was funded by the ELAN-Fonds der FAU Erlangen-Nurnberg (ELAN 12.01.02.1). Approval of ethics committee: (EK No. 45_12 Bc.). Results The metastatic lymph nodes showed in contrast to the non-metastatic lymph nodes a significantly ( p p Furthermore, the malignancy of the primary tumor (grading, T-, L- und Pn-status) is significantly ( p Conclusion Macrophage polarization and Gal-3 expression of the regional lymph nodes is significantly associated with parameters of malignancy of the primary tumor. This might resemble a tumor-derived peripheral immune tolerance.

Comparative analysis of cytokine transcript profiles within mediastinal lymph node compartments of pigs after infection with porcine reproductive and respiratory syndrome genotype 1 strains differing in pathogenicity.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces a weak immune response enabling it to persist in different organs of infected pigs. This has been attributed to the ability of PRRSV to influence the induction of cytokine responses. In this study, we investigated the cytokine transcriptional profiles in different compartments of the mediastinal lymph node of pigs infected with three genotype 1 PRRSV strains of differing pathogenicity: the low virulence prototype Lelystad virus (LV), and UK field strain 215–06 and the highly virulent subtype 3 SU1-Bel isolate from Belarus. We have used a combination of laser capture micro-dissection (LCM) followed by real time quantitative PCR (RT-qPCR) and immunohistochemical (IHC) detection of immune cell markers (CD3, CD79a and MAC387) and RT-qPCR quantification of PRRSV and cytokine transcripts. Compared to mock infected pigs, we found a significant downregulation of TNF-α and IFN-α in follicular and interfollicular areas of the mediastinal lymph node from 3 days post-infection (dpi) in animals infected with all three strains. This was accompanied by a transient B cell depletion and T cell and macrophage infiltration in the follicles together with T cell depletion in the interfollicular areas. A delayed upregulation of IFN-γ and IL-23p19 was observed mainly in the follicles. The PRRSV load was higher in all areas and time-points studied in the animals infected with the SU1-Bel strain. This paper describes the first application of LCM to study the cytokine transcript profiles and virus distribution in different compartments of the lymph node of pigs.

Pre-operative Ultrasound Diagnosis of Nodal Metastasis in Papillary Thyroid Carcinoma Patients According to Nodal Compartment

The aim of this study was to assess the accuracy of ultrasound (US) and individual US features in the diagnosis of nodal metastasis in patients with papillary thyroid carcinoma (PTC) with respect to nodal compartment. US diagnoses and individual US features of nodal metastases with respect to nodal compartment were investigated in 184 consecutive PTC patients who underwent pre-operative US. Histopathologic results were used as a reference standard. One hundred thirty-six of 368 (37.0%) central compartments contained one or more metastatic nodes, whereas 44 of 48 (91.7%) lateral compartments had one or more metastatic nodes. The malignancy rates of suspicious US diagnoses in the central and lateral compartments were 66.3% (53/80) and 93.3% (42/45), respectively. The central and lateral compartments differed significantly in nodal composition, echogenicity, calcification, shape, hilar echogenicity and vascularity. The accuracy of US in the diagnosis of nodal metastases from PTC was lower in the central compartment than in the lateral compartment.

Ultrasound Imaging of Nodal Metastases in the Central Compartment in Thyroid Cancer: is it Possible to Increase Sensitivity

Background and Purpose: Ultrasound imaging criteria for cervical lymph nodes were set mainly to increase sensitivity. However, unlike the lateral neck compartment, the challenge in the central compartment is the low sensitivity of Ultrasonography. We performed this study to evaluate whether the sensitivity of Ultrasonography could be increased by considering any detected lymph node in the central compartment as malignant. Methods: Forty one patients with differentiated thyroid cancer underwent dedicated pre-operative Ultrasonography by one radiologist for detection of metastatic lymph nodes in the central compartment. Any lymph node detected was considered positive regardless of Ultrasound morphologic criteria. All patients underwent thyroidectomy with central node dissection (CND), unilateral in 31 and bilateral in 10 cases, based on tumor size and laterality. Ultrasound imaging results were compared to histopathologic results. Results: The number of true positive cases by Ultrasonography was 13, false negative cases 8, true negative 15 and false positive 5 cases. The sensitivity of US was 61.9%, the specificity 75%, the positive predictive value 72.2% and the negative predictive value 65.2%. Conclusions: The sensitivity of Ultrasonography for detection of metastatic lymph nodes in the central compartment in patients with DTC may be increased, compared to previously published data, by considering every detected node as positive rather than using the routine criteria for lymph node metastases in other neck levels.

American Thyroid Association statement on preoperative imaging for thyroid cancer surgery.

The success of surgery for thyroid cancer hinges on thorough and accurate preoperative imaging, which enables complete clearance of the primary tumor and affected lymph node compartments. This working group was charged by the Surgical Affairs Committee of the American Thyroid Association to examine the available literature and to review the most appropriate imaging studies for the planning of initial and revision surgery for thyroid cancer. Ultrasound remains the most important imaging modality in the evaluation of thyroid cancer, and should be used routinely to assess both the primary tumor and all associated cervical lymph node basins preoperatively. Positive lymph nodes may be distinguished from normal nodes based upon size, shape, echogenicity, hypervascularity, loss of hilar architecture, and the presence of calcifications. Ultrasound-guided fine-needle aspiration of suspicious lymph nodes may be useful in guiding the extent of surgery. Cross-sectional imaging (computed tomography with contrast or magnetic resonance imaging) may be considered in select circumstances to better characterize tumor invasion and bulky, inferiorly located, or posteriorly located lymph nodes, or when ultrasound expertise is not available. The above recommendations are applicable to both initial and revision surgery. Functional imaging with positron emission tomography (PET) or PET-CT may be helpful in cases of recurrent cancer with positive tumor markers and negative anatomic imaging.

Central neck compartment dissection in papillary thyroid carcinoma: An update

Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy, accounting for approximatley 90% of thyroid malignancies in areas of the world without deficit of Iodine. It’s universally accepted that total thyroi­ dectomy is the minimal surgical treatment for patients with PTC higher than 1 cm. When a quality surgery is performed, the prognosis for PTC is excellent with 10 and 20-year overall survival rates around 90% and 85%, respectively. Lymph node metastases are very frequent in PTC, occurring in 50%-80% of PTC patients, the most of them being located in the central compartment of the neck (CCN) and with a high rate of occult or clinically undetectable disease. A lot of controversy exists regarding how to treat the central nodal compartment disease of PTC. The first problem is the lack of standardization of the terminology and concepts related to the CCN, which are clearly established and defined in this paper according to the most recent consensus documents of endocrine societies. This uniformity will provide a more consistent and clear communicaction between all the specialist involved in the treatment of PTC. CCN can be performed to treat patients with clinically detectable, radiologically suspected of intraoperative visualized nodal disease (this is defined as therapeutic) or when these findings are absent (also called prophylactic). Indicactions, advantages and disadvantages of both therapeutic and prophylactic CCN dissection are widely discussed and clear recommendations provided.

Increased malignancy of oral squamous cell carcinomas (oscc) is associated with macrophage polarization in regional lymph nodes - an immunohistochemical study.

BackgroundIt is largely accepted that specific immunological parameters in solid malignancies are associated with patient’s prognosis. Recently a correlation of macrophage polarization with histomorphological parameters could also be shown in oral squamous cell carcinoma (oscc). The observed tumor derived peripheral immune tolerance could be associated with the macrophage polarization in regional tumor draining lymph nodes.So far there are no studies analyzing the macrophage polarization in cervical lymph nodes of oscc patients. In the present study we aimed to correlate macrophage polarization in different anatomical lymph node compartments of patients diagnosed with oscc with histopathologic parameters of the primary tumor (T-, N-, L-, V-, Pn-status, grading).MethodsTumor free (n = 37) and metastatic (n = 17) lymph nodes of T1 and T2 oscc patients were processed for immunohistochemistry to detect CD68, CD11c, CD163 and MRC1 positive cells. Samples were digitized using whole slide imaging and the number of cells expressing the aforementioned markers in the region of interest quantitatively analyzed.ResultsThe malignancy of the primary tumor (defined by T-, L-, Pn-status, grading) correlated with the lymph node macrophage polarization. L1 and Pn1 tumor cases displayed a significantly (p < 0.05) decreased M1 and increased M2 polarization in the sinus of the lymph nodes. G3 cases presented a significantly (p < 0.05) increased M2 polarization in the sinus compared to G2 cases. T2 tumors had significantly (p < 0.05) increased M2 polarization in the interfollicular zone of regional lymph nodes compared to T1 tumors. Metastatic and non-metastatic lymph nodes did not differ regarding their macrophage polarization.ConclusionsThe current study revealed for the first time an influence of oscc on the macrophage polarization in regional lymph nodes. Markers of malignant behavior in the primary tumor were associated with a shift of macrophage polarization in lymph nodes from the anti-tumoral M1 type to the tumor-promoting M2 type. As tumor free and metastatic lymph nodes did not differ in terms of their macrophage polarization pattern, there must be other factors influencing the location for lymph node metastasis formation.