Presence Of Lymphocytic Infiltration Research Articles

Lymphocytic Infiltration as a Prognostic Factor in Patients With Colon Cancer.

Host-defense mechanisms may have an important role in predicting the outcome of colorectal cancer patients. We designed our study to evaluate the possible prognostic significance of the presence of lymphocytic infiltration (LI) and subgroups of lymphocytes (CD3 and CD20) in the primary tumors. We randomly selected 195 patients operated for colorectal carcinoma from a larger cohort of 1527 patients with colorectal cancer. Histological slides were blindly reevaluated for the presence of LI that was graded 0 to 3. Immunohistochemical phenotyping of the lymphocytes was performed only for tumors with LI score 3 and included antibodies CD3 and CD20. CD3 and CD20 immunostaining were graded in the same manner as LI. The mean duration of follow-up was 63.8 months. The distribution of patients with colorectal cancer according to LI scores was as follows: score 0, 20/195 (10.2%); score 1, 61/195 (31.3%); score 2, 78/195 (40%); and score 3, 36/195 (18.5%). There was no correlation between any clinicopathological pattern and LI. Score 3 staining for CD3 was more common than for CD20 (64.7% vs 8.8%, P < .0001). Prominent lymphocytic infiltration (score 3) was associated with better disease-free survival (P = .062). Recurrence was diagnosed among 2/22 (9.1%) patients with prominent CD3 staining versus 62/171 (36.2%) of all other patient groups (P = .054) and they correspondingly had better disease-free survival (P = .018). It seems we can identify a group of patients with colorectal cancer who have an excellent prognosis according to a single immunological test unrelated to other known prognostic factors.

Halo Nevus ? the Vascular Connection

Abstract Background: Halo Nevi (HN), are defined as benign melanocytic nevi that are surrounded by a rim of depigmentation, resembling a halo. The halo phenomenon indicates the involution and subsequent regression of the melanocytic nevus. Material and Methods: A random series of 137 nevi, including 75 HN were examined. Serial paraffin and frozen sections were subjected to: routine histochemistry; (HE, Reticulin, Auro, PAS), enzyme histochemistry: dopa oxidase, counterstained with Nuclear Fast Red (NFR) to highlight the endothelium and dopamine oxidase; immunohistochemistry to assess presence of lymphocytic infiltrates; electron microscopy: after enbloc dopa stain. Results and Discussion: Junctional nevi show proliferation of highly dendritic melanocytes within the epidermis. Intradermal nevi are composed of dermal nevus cells separated from the epidermis by a clear Grenz zone. Compound nevi show a combination of junctional activity and sheets of dermal nevus cells. Some nevi show a depigmented halo and can regress completely to be replaced by a depigmented patch, the halo nevus. The nevus cells and marginal melanocytes are replaced by endothelial cells, lining vascular spaces, with involution of the nevus. Intriguingly there is a complete absence of inflammatory and immune related lympho-histiocytic cells in the cases studied. These observations, suggest that nevus cells are replaced by vascular endothelial cell types which results in dissolution of the lesion.

Obstructive Sleep Apnea and Lymphocytic Sialadenitis: The Focus isn’t Just Sjögren’s Syndrome

Objective: We examined the presence of lymphocytic infiltration and measured focus scores in uvular specimens of patients with obstructive sleep apnea (OSA). Methods: We reviewed the histopathology of 101 uvular specimens obtained from patients with OSA and uvular hypertrophy. A lymphocyte focus score assessment was performed for each case. Results: Of the 101 cases, 42 (42%) cases had a positive focus score (score ≥ 1). Of those cases with a positive focus score, 22 (52%) had a focus score of 1, 14 (33%) had a focus score of 2, 4 (9%) had a focus score of 3, and 2 (5%) had a focus score of 4. Of the 59 patients (58%) with negative focus scores, 39 (66%) had minor lymphocytic infiltrates; 17 (29%) had features of chronic sialadenitis or extensive fibrosis; 3 (5%) had salivary mucosa without any apparent lymphocytes. Conclusion: Our findings indicate that patients with OSA may exhibit focal lymphocytic sialadenitis (FLS). It remains to be determined whether mucosal changes occur elsewhere in the oral cavity of patients with OSA. If so, the presence of OSA may complicate the histologic evaluation of Sjogren’s syndrome. Further investigations to determine the prevalence of FLS in the uvulae of individuals without history of OSA, the extent of FLS elsewhere within the oral cavity of patients with OSA and the relationship between the local inflammatory reaction and the systemic consequences of OSA are needed.

Th17/Treg cells imbalance and GITRL profile in patients with Hashimoto's thyroiditis.

Hashimoto’s thyroiditis (HT) is an organ-specific immune disease characterized by the presence of lymphocytic infiltration and serum autoantibodies. Previous studies have confirmed the critical role of Th17 cells in the pathopoiesis of HT patients. Additionally, regulatory T cells (Treg) display a dysregulatory function in autoimmune disease. The purpose of this study is to investigate the alteration of Th17 and Treg cells in HT patients and explore contributing factors. We found there was an increased ratio of Th17/Treg in HT patients and a positive correlation with autoantibodies (anti-TgAb). In addition, there was an increased level of GITRL, which has been demonstrated to be correlated with the increassement of Th17 cells in the serum and thyroid glands of HT patients; the upregulated serum level of GITRL has a positive correlation with the percentage of Th17 cells in HT patients. In summary, an increase in GITRL may impair the balance of Th17/Treg, and contribute to the pathopoiesis of Hashimoto’s thyroiditis.

Interferon-γ induces immunoproteasomes and the presentation of MHC I-associated peptides on human salivary gland cells.

A prominent histopathological feature of Sjögren's syndrome, an autoimmune disease, is the presence of lymphocytic infiltrates in the salivary and lachrymal glands. Such infiltrates are comprised of activated lymphocytes and macrophages, and known to produce multiple cytokines including interferon-gamma (IFN-γ). In this study, we have demonstrated that IFN-γ strongly induces the expression of immunoproteasome beta subunits (β1i, β2i and β5i) and immunoproteasome activity but conversely inhibits the expression of proteasome beta subunits (β1, β2 and β5) in human salivary gland (HSG) cells. Mass spectrometric analysis has revealed potential MHC I-associated peptides on the HSG cells, including a tryptic peptide derived from salivary amylase, due to IFN-γ stimulation. These results suggest that IFN-γ induces immunoproteasomes in HSG cells, leading to enhanced presentation of MHC I-associated peptides on cell surface. These peptide-presenting salivary gland cells may be recognized and targeted by auto-reactive T lymphocytes. We have also found that lactacystin, a proteasome inhibitor, inhibits the expression of β1 subunit in HSG cells and blocks the IFN-γ-induced expression of β1i and immunoproteasome activity. However, the expression of β2i and β5i in HSG cells is not affected by lactacystin. These results may add new insight into the mechanism regarding how lactacystin blocks the action of proteasomes or immunoproteasomes.

PARANEOPLASTIC NEUROLOGICAL DISORDERS

Paraneoplastic Neurological Disorders (PND) are uncommon but important because they frequently present before a cancer is diagnosed and because they cause severe neurological disability. Current thinking is that they are...

A Review of Lupus Miliaris Disseminatus Faciei-Like Histopathologic Changes in 10 Cases

Objective: To determine the clinical and histopathologic features of all lesions diagnosed as lupus miliaris disseminatus faciei via biopsy over the past 16 years at a single institution. Clinical features reviewed included age of patient, location and number of lesions, duration, description of primary lesion, size, and suspected clinical diagnosis or differential diagnosis. Histopathologic features reviewed included presence of caseation necrosis, depth of granuloma, presence of lymphocytic infiltrate, disruption of hair follicles, and presence of multinucleated giant cells. Methods: The records of 10 patients (mean age, 50.4 years; range, 6 to 79 years) with characteristic histologic features of lupus miliaris disseminatus faciei were reviewed and the histopathologic findings and clinical features were analyzed. Formalin-fixed, paraffin-embedded specimens were examined by hematoxylin-eosin staining. Results: The most common clinical appearance was a single papule located on the face. Two cases with solitary, extrafacial distributions were reported. All cases demonstrated epithelioid granulomas with a central area of caseation necrosis. The majority of granulomas were perifollicular in location and were comprised of histiocytes, lymphocytes, and multinucleated giant cells. Conclusion: The 10 cases we report demonstrate the importance of recognizing the entity in solitary as well as extrafacial forms. Limiting the histologic diagnosis to fully developed lesions demonstrating epithelioid granulomas with caseation necrosis serves to clarify the diagnosis in the setting of diverse clinical presentations. Further information is needed to clarify the diagnosis, etiology, and pathogenesis of this disease, but an unusual host response to folliculitis or follicular injury likely plays a role in most cases.

Transcriptional Hallmarks Of Tumor Infiltrating Lymphocyte Responses To Melanoma

Tumor-infiltrating lymphocytes (TIL) are found in a subset of melanomas. Patients with pronounced TIL responses have an excellent prognosis, suggesting that for those patients, the infiltrating immune cells are part of an effective adaptive and/or innate response to cancer. However, the molecular features of brisk TIL infiltrates have not been analyzed in situ. Moreover, it is not clear whether the features of the immune response to melanoma are shared by other tumors. Here, we used histological grading of TIL infiltrates in melanoma samples from The Cancer Genome Atlas combined with analysis of immune signatures in transcriptional profiles from the same tumors to characterize the molecular features of the immune response to melanoma. To categorize the histological grade of immune infiltrate, we reviewed digital images of 156 melanoma samples, and assigned a TIL grade (0 - 3) based on established criteria. We found that the distribution of TIL grades in our dataset was consistent with previously published analyses. We first tested whether tumors with brisk infiltrate (TIL Grade 2 or 3) showed enrichment of immune signatures relative to those with non-brisk infiltrates (TIL Grade 0 or 1) using gene-set enrichment analysis (GSEA) with a collection of ∼2000 immune-related gene-sets manually curated from published studies of adaptive and innate immunity. We found that 493 immune signatures enriched in brisk tumors (FDR<0.25), while none enriched in non-brisk tumors, suggesting that the histological TIL grade was strongly associated with transcriptional features of an immune response. Gene-sets that enriched in tumors with brisk infiltrates included those derived from CD4 and CD8 T cells (evidenced by increased expression of T cell lineage-specific genes such as CD3G, ZAP70, CD28, TBX21, PRDM1, GZMB, PRF1); those related to monocytes (CD14); as well as Type I interferon response genes (OAS1, IFI44). Surprisingly we did not find enrichment of gene-sets related to CD8 T cell exhaustion. Instead, we found highly significant enrichment of effector CD8 T cell gene-sets that featured effector cytokines, such as IFNG and TNF, and cytokine receptors such as IL-15R and IL-2RB, genes that which are normally decreased in expression in exhausted T cells. This suggests that the transcriptional profile of brisk immune infiltrates in melanoma includes features of highly functional CD8 effector T cell responses and lacks transcriptional features of exhaustion. We next tested whether the signatures of immune response to melanoma were enriched in other tumors. We identified a core set of “TIL hallmark genes” comprised of GSEA leading-edge genes from multiple gene-sets enriched in brisk vs. non-brisk melanoma samples. We then grouped the gene expression profiles of other tumor histologies according to their expression of TIL hallmark genes using single-sample GSEA. In thyroid cancer, for example, we found that the enrichment of melanoma TIL hallmark genes was strongly correlated with the presence of lymphocyte infiltrates, suggesting that there are common features of the immune response to cancer in different tumor types. Our results show that integrated analysis of histology and gene expression profiles from melanoma samples can identify the molecular features of the TIL response. We find evidence for signatures of effective CD8 T cell responses in brisk infiltrate melanomas that are shared by other tumor types. These TIL hallmark genes may help identify molecular subsets of immunogenic tumors, providing novel outcome predictors, and opportunities to stratify immunotherapeutic treatment options. More broadly, this approach can help deconvolve tumor/host gene expression profiles and better characterize the human immune response to cancer. Disclosures:No relevant conflicts of interest to declare.

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation, oxidative stress, and differential morphological changes in the mouse lung

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D.

BRAF V600E assessment by pyrosequencing in fine needle aspirates of thyroid nodules with concurrent Hashimoto’s thyroiditis is a reliable assay

Detection of BRAF mutation in cytology specimens has been proposed as a diagnostic adjunctive tool in evaluation of thyroid nodules with indeterminate cytology findings. Concurrent papillary thyroid carcinoma and Hashimoto's thyroiditis (HT), a disease characterized by thyroid lymphocytic infiltration, is a frequent occurrence. A large lymphocytic infiltrate might reduce the sensitivity of methods employed to detect BRAF mutation in thyroid cytology specimens. To determine whether testing for BRAF mutational status in fine needle aspirates (FNA) is reliable also in the presence of HT lymphocytic infiltration, we assessed the BRAF status by direct sequencing and pyrosequencing in a series of FNAs with and without concomitant HT lymphocytic infiltration. We also performed the same assessment by pyrosequencing in the corresponding tissue samples. Pyrosequencing demonstrated to be more sensitive than direct sequencing. The percentage of mutant BRAF(V600E) alleles was higher in FNAs than in the corresponding tissues, probably because of the lower stromal contamination in FNA than in the sections. In the presence of lymphocytic infiltration, the percentage of mutant BRAF(V600E) alleles determined by pyrosequencing was higher in FNAs than in the corresponding tissue samples (P < 0.0001), indicating a minor lymphocytic contamination in FNA. The diagnostic value of BRAF(V600E) in inconclusive FNAs was not hampered by thyroid lymphocytic infiltration. These results indicate that BRAF(V600E) assessment by pyrosequencing is a reliable assay useful to refine inconclusive cytology of thyroid nodules also in the presence of concurrent HT.

Protective effect of a mixture of kefir-isolated lactic acid bacteria and yeasts in a hamster model of Clostridium difficile infection

The objective of this work was to test the protective effect of a mixture (MM) constituted by kefir-isolated microorganisms (Lactobacillus plantarum, Lactobacillus kefir, Lc. lactis, Kluyveromyces marxianus and Saccharomyces cerevisiae) in a hamster model of infection with Clostridium difficile, an anaerobic Gram-positive bacterium that causes diarrhoea. Placebo or MM was administered ad libitum in drinking water from day 0 to the end of treatment. Hamsters received orally 200 μg of clyndamicin at day 7 and then were infected with 1 × 108 CFU of C. difficile by gavage. Development of diarrhoea and death was registered until the end of the protocol. Surviving animals were sacrificed at day 16, and a test for biological activity of clostridial toxins and histological stainings were performed in caecum samples. Six of seven infected animals developed diarrhoea and 5/7 died at the end of the experimental protocol. The histological sections showed oedema and inflammatory infiltrates with neutrophils and crypt abscesses. In the group of animals infected and treated with MM1/1000, only 1 of 7 hamsters showed diarrhoea and none of them died. The histological sections showed only a slight thickening of the mucosa with presence of lymphocytic infiltrate. These results demonstrate that an oral treatment with a mixture of kefir-isolated bacteria and yeasts was able to prevent diarrhoea and enterocolitis triggered by C. difficile.

DARC (Duffy) and BCAM (Lutheran) reduced expression in thyroid cancer

Duffy or DARC (Duffy Antigen Receptor for Chemokines) is a glycosylated membrane protein that selectively binds angiogenic chemokines. Previous in vivo and in vitro studies of DARC function in cancer have associated DARC over expression with better prognosis, decreased metastatic potential, and inhibition of tumor-associated neovascularization. Another carcinogenesis-associated antigen is Lutheran or BCAM (basal cell adhesion molecule), a surface glycoprotein that acts as a receptor for the extracellular matrix protein, laminin. BCAM is a protein related to tumor progression; and, its over expression is associated with skin, ovarian and pancreatic cancers. We explored DARC and BCAM functions and investigated whether or not their expressions were altered in thyroid cancer. The expression of DARC and BCAM were evaluated by quantitative real-time PCR (qPCR) in a set of 18 normal thyroid tissues (NT), 15 follicular adenomas (FTA), 17 follicular carcinomas (FTC), and 122 papillary thyroid carcinomas (PTC), including 78 classical (CVPTC) and 44 follicular variant (FVPTC). RNA was isolated, reverse transcribed to cDNA, and used in qPCR reactions containing SYBR Green. The relative expression value was calculated using ribosomal protein S8 as an internal control. When we compared benign (NT and FTA) versus malignant samples (FTC, CVPTC and FVPTC) we observed a significant decrease of DARC and BCAM relative expression in malignant cases. Additionally, we correlated clinic-pathological features (tumor size, presence of metastasis, presence of lymphocyte infiltrate) with DARC and BCAM expression. We found a diminished expression of DARC in PTC samples, which was correlated with tumor size and presence of a lymphocyte infiltrate. We, also, found a correlation between decreased BCAM expression and tumor size or presence of metastasis. DARC and BCAM expression was associated with pathogenesis of thyroid carcinoma and correlated with clinical-pathological features.

Polyglandular Autoimmune Syndrome Type II

The polyglandular autoimmune syndromes (PAS) comprise a wide spectrum of autoimmune disorders. There exist a juvenile (PAS I) and an adult type (PAS II). The nature of PAS has been based on the presence of lymphocyte infiltration in the affected gland, organ-specific antibodies in the serum, cellular immune defects and an association with the human leucocyte antigen (HLA) DR/DQ genes or immune response genes. Autoantibodies to the various endocrine and non-endocrine tissues not only offer a diagnostic clue to the autoimmune nature of diseases but also can be used to identify asymptomatic individuals who are at risk of developing other component diseases of the syndrome. Although target tissues or glands differ, several common threads link the diseases of PAS. A defect resides in one of the genes of the HLA locus which, in concert with other gene(s), results in susceptibility. Genetic susceptibility is necessary but not sufficient to produce the disorder. This is illustrated by the lack of 100% concordance of disease in identical twins. Genetic testing may identify patients with PAS I, but not those with PAS II. For PAS II, susceptibility genes are known which increase the risk for developing autoimmune disorders, but must not be causative. These are certain HLA genes, the cytotoxic T-lymphocyte antigen (CTLA-4) gene, and the protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes on chromosomes 6, 2, and 1, respectively. When the genetic defects and environmental influences of organ-specific autoimmunity are better understood, it may be possible to devise specific replacement or corrective therapies. Given the similar features of many of the organ-specific autoimmune disorders, it is likely that if immunotherapeutic modalities are successful in one disease, they may be of benefit in related disorders.

Focal pseudohypertrophy of the left hemi-tongue

A 72 year-old man with a history of diabetes mellitus noticed that his tongue deviated to the left when it was stuck out. He consulted our hospital since this feature persisted for 9 months. The diabetes mellitus was well controlled by voglibose (0.6 mg/day) and gliclazide (80 mg/day), and serum levels of glucose and glycated hemoglobin were 104 mg/dl and 6.1%, respectively. The patient had no signs of neurologic involvement attributable to diabetes mellitus. The left side of the tongue was hypertrophic and the tongue deviated to left (Fig. 1). Left hemi-tongue weakness was evident. There was no fasciculation, and deep tendon reflexes were normal, with no pathological reflexes. The results of other neurological examinations including swallowing, speaking and tasting were negative. Electromyography of the left side of the tongue showed neuropathic motor unit action potentials, polyphasic motor unit potentials, positive sharp wave and fibrillation potentials. The number of motor units per second was decreased. The right side of the tongue showed none of these findings. All other muscles examined (deltoid, biceps, triceps, adductor of thumb, quadriceps, gastrocnemius, and tibialis anterior) showed no evidence of neuropathic or myopathic motor unit action potentials. Magnetic resonance imaging (MRI) of the tongue revealed markedly increased signal intensity in the left side of the tongue on T1-weighted images (Fig. 1a, c) and T2weighted images (Fig. 1b). The left side of the tongue was enlarged. Contrast-enhanced, T1-weighted MRI images obtained with the use of a bolus of gadoliniumdiethylenetriamine pentaacetic acid showed a circular lesion with ringed enhancement in the root of the left side of the tongue (Fig. 1d, white arrow). Intracranial abnormal signals including the brainstem were not evident on MRI. Anti-IL2 receptor antibody (303 U/ml), antinuclear antibody, and M-protein on immunoelectrophoresis were negative. Hypertrophy of the root of the left side of the tongue was evident on laryngoscopy. A biopsy of the root of the tongue showed lymphocyte infiltration with no malignant cells. Monoclonality was absent on immunohistochemical studies. One year later, short inversion time inversion recovery (STIR) images on repeated MRI showed the decreased signal intensity in the left hemitongue with increased signal intensity on T1-weighted images and T2-weighted images. The size of the circular lesion with ringed enhancement was unchanged. On the basis of the ringed enhancement on MRI and the presence of lymphocyte infiltration with no malignancy on histopathological examination, the lesion was diagnosed to be an inflammatory cystic lesion ‘‘abscess’’. On 20 months after consultation to our hospital, the left hemi-tongue weakness was static. These findings could be explained by denervation and reinnervation or by increasing frequencies of motor unit firing from the left hypoglossal nerve and adjacent motor fibers, which were impaired by the cystic lesion in the left side of the tongue. Neuralgic muscle hypertrophy of the limbs has been reported in several types of lower motor neuron disease, such as multifocal motor neuropathy [1], Guillain-Barre syndrome [1], and radiculopathy [3, 4], but such hypertrophy involving cranial nerves has not been reported previously to our knowledge. Prior studies suggest that continuous, spontaneous electrical activity of a muscle associated with disease conditions can cause neuralgic H. Kataoka (&) S. Ueno Department of Neurology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan e-mail: hk55@naramed-u.ac.jp

Higher Intratumoral Expression of CD1a, Tryptase, and CD68 in a Follicular Variant of Papillary Thyroid Carcinoma Compared to Adenomas: Correlation with Clinical and Pathological Parameters

In a number of human malignancies, the presence of lymphocytic infiltration in or around tumor tissue is commonly considered to be part of the host tumor immune response. An association between thyroid carcinoma and chronic inflammation has been described. This relationship is not fully understood, so we performed a systematic study on a follicular variant of papillary thyroid carcinoma (FVPTC), to evaluate the type and distribution of certain immunological cells and their relationship with prognostic factors. We selected 91 consecutive cases of FVPTC, in which we evaluated the presence of three different immunological cells: dendritic cells (DC), immature CD1a+ and mature DC-Lamp+; mast cells (MC), tryptase+; and macrophages (M), CD68+, in the intratumoral, peritumoral, and extratumoral areas. As a control we analyzed 44 cases of thyroid adenomas (A). In the intratumoral and peritumoral areas, the expression of CD1a, tryptase, and CD68 was significantly higher in FVPTC than in adenomas. Expression of CD1a and tryptase was comparable in the extratumoral compartment, whereas CD68 expression in the extratumoral area was significantly higher in FVPTC than in adenoma (p=0.0015). DC-Lamp expression was not significantly different among the intra-tumor, peri-tumor, and extra-tumor areas of FVPTC or adenoma. It was also very interesting that nonencapsulated FVPTC were more positive to tryptase. We highlight a higher presence of immunological cells in carcinomas than in adenomas. On this basis, it is possible to speculate that these inflammatory elements could be involved in tumor progression and invasion, as appears to be the case for MC and M.

Local Cell Mediated Immune Reaction in Primary Obstructive Male Infertility

Increased intra-epididymal pressure due to obstruction causes a breach in the epididymal lining exposing the highly antigenic sperms to the interstitium. When the exposure is small and intermittent, it is likely to induce a local humoral response which may affect sperm maturation and also react with the epididymal epithelium producing irreversible histological changes. The present study on 30 patients of primary obstructive infertility found direct and indirect evidence of the production of antisperm antibodies locally. ELISA for antisperm antibodies was positive in the epididymal fluid in 16/30 (53%) of the patients. Indirect evidence of the role of local antigen-antibody reaction in the epididymis is apparent in 22/30 (73%) patients who had a lymphocytic infiltrate. The local presence of antisperm antibodies in the epididymal fluid correlated well with the presence of lymphocytic infiltration in the interstitium (p < 0.05). In our study 16/30 patients had a positive ELISA for antisperm antibody and all these patients had interstitial lymphocytic infiltration. In addition eight patients with a negative ELISA also showed interstitial lymphocytic infiltration. Thus 22/30 (73%) patients had an evidence of a local immune reaction directly in the form of a positive ELISA for antisperm antibodies in the epididymal fluid and / or indirect evidence in the form of lymphocytic infiltrate in the interstitium. None of the five controls had either a positive ELISA or lymphocytic infiltrate, this difference was found to be statistically significant (p < 0.005).

Expectation–Maximization-Driven Geodesic Active Contour With Overlap Resolution (EMaGACOR): Application to Lymphocyte Segmentation on Breast Cancer Histopathology

The presence of lymphocytic infiltration (LI) has been correlated with nodal metastasis and tumor recurrence in HER2+ breast cancer (BC). The ability to automatically detect and quantify extent of LI on histopathology imagery could potentially result in the development of an image based prognostic tool for human epidermal growth factor receptor-2 (HER2+) BC patients. Lymphocyte segmentation in hematoxylin and eosin (H&E) stained BC histopathology images is complicated by the similarity in appearance between lymphocyte nuclei and other structures (e.g., cancer nuclei) in the image. Additional challenges include biological variability, histological artifacts, and high prevalence of overlapping objects. Although active contours are widely employed in image segmentation, they are limited in their ability to segment overlapping objects and are sensitive to initialization. In this paper, we present a new segmentation scheme, expectation-maximization (EM) driven geodesic active contour with overlap resolution (EMaGACOR), which we apply to automatically detecting and segmenting lymphocytes on HER2+ BC histopathology images. EMaGACOR utilizes the expectation-maximization algorithm for automatically initializing a geodesic active contour (GAC) and includes a novel scheme based on heuristic splitting of contours via identification of high concavity points for resolving overlapping structures. EMaGACOR was evaluated on a total of 100 HER2+ breast biopsy histology images and was found to have a detection sensitivity of over 86% and a positive predictive value of over 64%. By comparison, the EMaGAC model (without overlap resolution) and GAC model yielded corresponding detection sensitivities of 42% and 19%, respectively. Furthermore, EMaGACOR was able to correctly resolve over 90% of overlaps between intersecting lymphocytes. Hausdorff distance (HD) and mean absolute distance (MAD) for EMaGACOR were found to be 2.1 and 0.9 pixels, respectively, and significantly better compared to the corresponding performance of the EMaGAC and GAC models. EMaGACOR is an efficient, robust, reproducible, and accurate segmentation technique that could potentially be applied to other biomedical image analysis problems.

Influence of lymphocitic thyroiditis on prognostic outcome differentiated thyroid carcinoma

Thyroid carcinoma is rare malignant tumors. They are typically presented with slow progression and clinical course. Lymphocytic infiltration, including fagocytosis of neoplastic cells by macrophage plays an important role in preventing development of distant metastases. This paper sets the following objectives: Establish whether presence or absence of Hashimoto thyroiditis in differentiated thyroid carcinoma (DTC) is a favourable prognostic factor. The group under examination here are all newly diagnosed patients with differentiated thyroid carcinoma surgically treated at the Surgery Clinic in Podgorica from 2003. to 2010. A total of 125 patients, aged 11 to 79, were included in this research. The patients were divided in two groups, those with and those without lymphocytic infiltration. Both groups were mutually compared for their prognostic factors. For the identification of T and B lymphocytes, anti-CD 3 and anti-CD 20 antibodies were used. Student t-test was used for comparison of clinical and pathological parameters among groups, Hi square test for comparison of frequency, and Coxs regression model for time dependant variables as frequency of recurrence among groups with various stages of disease. Survival curve (Kaplan-Meier) is used for comparison of time dependant variables (survival, recurrence, death). The follow-up time ranges from 10 to 70 months in both groups of patients. presence of lymphocytic infiltration in thyroid tissue in patients with differentiated thyroid carcinoma is significant prognostic factor (P < 0.0001). But, absence of lymphocytic infiltration is a poor prognostic factor in patients with invasive extra thyroid tumours (P < 0.0001). Also, absence of lymphocytic infiltration is a poor prognostic factor for development of lymphogenic and hematogenic metastases. The presence of T or B lymphocytes and varying degree of their presence is not a significant prognostic factor (P < 0.0046). Patients without lymphocytic infiltration are significantly more numerous in the fourth stage of disease (P < 0.0001). There is no statistically significant difference in terms of the presence of T or B lymphocytes in the tissue. Chronic lymphocytic thyroidis hahshimoto is a favourable prognostic factor in our examined group (P < 0.0001). Local invasiveness and extrathyroid expansion is significantly smaller in the group of patients with the presence of lymphocytic infiltration (P < 0.0001). By means of univariate analysis, we found that factors with a significant impact on survival rate include age (P < 0.0001), size of tumour (P < 0.018), extrathyroid invasiveness (P < 0.0001), hematogenic metastases (P < 0.049). Lymphocytic infiltration is present in 81% of patients in their thyroid gland, and in 19% patients there are no lymphocytes in tissue. Limphocitic infiltration has a favourable influence on tumor variables. CONCLUSION. This research has shown that lymphocytes in tissue as part of Hashimoto thzroiditis have an effect on certain prognostic factors of differentiated thyroid carcinoma as size, smaller invasiveness and extrathyroid tumour growth and incidence of hematogenic metastases.

Computerized Image-Based Detection and Grading of Lymphocytic Infiltration in HER2+ Breast Cancer Histopathology

The identification of phenotypic changes in breast cancer (BC) histopathology on account of corresponding molecular changes is of significant clinical importance in predicting disease outcome. One such example is the presence of lymphocytic infiltration (LI) in histopathology, which has been correlated with nodal metastasis and distant recurrence in HER2+ BC patients. In this paper, we present a computer-aided diagnosis (CADx) scheme to automatically detect and grade the extent of LI in digitized HER2+ BC histopathology. Lymphocytes are first automatically detected by a combination of region growing and Markov random field algorithms. Using the centers of individual detected lymphocytes as vertices, three graphs (Voronoi diagram, Delaunay triangulation, and minimum spanning tree) are constructed and a total of 50 image-derived features describing the arrangement of the lymphocytes are extracted from each sample. A nonlinear dimensionality reduction scheme, graph embedding (GE), is then used to project the high-dimensional feature vector into a reduced 3-D embedding space. A support vector machine classifier is used to discriminate samples with high and low LI in the reduced dimensional embedding space. A total of 41 HER2+ hematoxylin-and-eosin-stained images obtained from 12 patients were considered in this study. For more than 100 three-fold cross-validation trials, the architectural feature set successfully distinguished samples of high and low LI levels with a classification accuracy greater than 90%. The popular unsupervised Varma-Zisserman texton-based classification scheme was used for comparison and yielded a classification accuracy of only 60%. Additionally, the projection of the 50 image-derived features for all 41 tissue samples into a reduced dimensional space via GE allowed for the visualization of a smooth manifold that revealed a continuum between low, intermediate, and high levels of LI. Since it is known that extent of LI in BC biopsy specimens is a prognostic indicator, our CADx scheme will potentially help clinicians determine disease outcome and allow them to make better therapy recommendations for patients with HER2+ BC.

A case of syringotropic cutaneous T-cell lymphoma treated with local radiotherapy

Syringotropic cutaneous T-cell lymphoma (SCTCL) is a variant of mycosis fungoides that is characterized by the presence of lymphocytic infiltration of eccrine glandular structures and the absence of the classic features of MF, such as epidermotropism and Pautrier's microabscesses. We report a patient with SCTCL who presented with multiple hypopigmented patches and localized alopecia who was treated with local radiotherapy with excellent local control. In our experience, local electron radiation offers local control in early stage SCTCL, and it may be possible to reserve systemic therapy for more advanced stages of the disease.