High frequency of virus-specific B lymphocytes in germinal centers of simian-human immunodeficiency virus-infected rhesus monkeys

The etiology of the lymphadenopathy and follicular hyperplasia associated with human immunodeficiency virus type 1 (HIV-1) infection has remained unclear. To determine whether the B-lymphocyte expansions characteristic of this syndrome represent polyclonal and virus-specific processes, the antigen specificity of B cells in lymphoid tissues of monkeys infected with simian-human immunodeficiency virus (SHIV) chimeras was assessed using an inverse immunohistochemical assay with biotinylated HIV-1 envelope gp120 (Env) as an antigen probe. Env-binding B cells were found aggregated in lymph node and splenic germinal centers (GCs). Most Env-binding GCs also contained an unstained population of B cells, suggesting the GCs were formed by a polyclonal (oligoclonal) process. By day 42 following infection, Env-binding B cells were present in 19% of all lymph node GCs. Env-binding cells were present in 25% of GCs even during chronic infection. This extraordinarily high frequency of Env-specific B lymphocytes suggests that the expansion of virus-specific B cells may largely account for the follicular hyperplasia in AIDS virus-infected individuals.     

Fine needle aspiration cytology of benign lymph node hyperplasias. Diagnostic significance of lymphohistiocytic aggregates

The fine needle aspiration cytomorphology and the number of lymphohistiocytic aggregates were correlated with five categories of benign lymph node histologies. Of 187 patients who had benign lymph node aspiration diagnoses made from 1975 to 1982 at the Medical College of Virginia, 26 had a subsequent lymph node biopsy. Excluded from the study were four cases with the biopsy site different from the aspiration site, three cases with evidence of metastatic carcinoma and one case of fistula at the site of biopsy. Of the remaining 18 cases, 13 (72%) had lymphohistiocytic aggregates on the aspiration slides. The mean number of lymphohistiocytic aggregates on the aspiration slides was greater in cases with histologic evidence of follicular hyperplasia (6.1) than in those with some other predominating benign histology (1.6).     

DNA measurements in thin sections of lymphomas

The DNA content of the nuclei of lymphomas and a reactive lymph node was studied by light absorption measurements in Feulgen-stained thin (2 microns) sections of lymph node biopsies, using the TAS image analysis system. For each nucleus, the integrated light absorbance at 548 nm wavelength was multiplied by the square root of the nuclear area to obtain a parameter for DNA independent from the nuclear size. In a hyperplastic reactive lymph node with follicular hyperplasia, the distribution of DNA X square root area was different in centrocytes and centroblasts, being compatible with a diploid centrocyte fraction and a mainly tetraploid centroblast fraction, in which hypertetraploid (octoploid?) nuclei were present. Similar measurements in three follicular centroblastic-centrocytic lymphomas gave similar results, with the centroblasts mainly tetraploid. The DNA distribution was studied in sections of lymphomas of high and low grades of malignancy, classified visually on the number of mitoses seen per field. The distribution width, from the smoothed histogram as the DNA X square root area values beyond the maximum peak frequency, appeared to be larger in the high-grade malignant lymphomas, in accordance with their higher number of mitoses.     

Cutaneous tumour of northern pike Esox lucius L.: evidence for a monocytic neoplasm

An epidemic of cutaneous tumours occurs in northern pike from the Åland Islands of Finland. Lymphocytes of pike could be triggered to synthesize DNA in vitro by mitogens. Tumour cells had a high basic metabolic rate and mitogens did not enhance their incorporation of ³H-thymidine. High percentages of peripheral blood, spleen, and head kidney mononuclear cells were surface (SIg) and cytoplasmic (CIg) immunoglobulin-positive by indirect immunofluorescence, using rabbit anti-pike IgM antibodies. Lower but still substantially high percentages of SIg and CIg immunofluorescence were observed with mouse anti-carp IgM antibodies. Tumour cells, however, were SIg- and Clg-negative, suggesting that the neoplasm is not a B cell lymphoma or plasmacytoma. A majority of tumour cells exhibited an intense diffuse staining pattern for alpha-naphthyl acetate esterase which was inhibited by sodium fluoride and was reminiscent of that in human monocytes. By electron microscopy (EM), the tumour cells were seen to be closely apposed with a lack of cell-cell junctions, and characteristically contained groups of lysosomes and large numbers of cytoplasmic lipid droplets, which are features of histiomonocytic cells. Although the marker studies do not completely rule out a T-lymphocytic origin, we suggest that the EM findings lend support for the view that the Åland pike neoplasm may be derived from the monocytic lineage.     

Metallic tin-induced lymphadenopathy in rat strains and hybrids

Metallic tin powder, injected into Lewis rats obtained from three different sources, caused enlargement of the regional draining lymph nodes. The histopathology featured epithelioid cell granulomas around phagocytosed particles of tin and an intense hyperplasia of plasma cells. The same material injected into August rats enlarged the lymph nodes but the enlargement was caused by granulomas without a major concomitant plasma cell response. In most other strains, tin produced less lymph node enlargement and the plasma cell response was minimal. However, F1 hybrids of Lewis rats with either the August, Brown-Norway (BN), or Dark Agouti (DA) strains developed plasma cell hyperplasia similar to that seen in the parental Lewis strain. The response to tin was the same whether the tin was injected into the feet or into the peritoneal cavity. Thus, the lymph node response to metallic tin varied from a slight, banal response to insoluble foreign particles, to an exuberant granulomatous hyperplasia, to an intense plasmacellular hyperplasia, depending on the genetic characteristics of the subjects.     

Human follicular dendritic cells express CR1, CR2, and CR3 complement receptor antigens

The expression of complement receptors by human follicular dendritic cells (FDC) was investigated by immunohistochemical techniques by using polyclonal and monoclonal antibodies to antigenic determinants of CR1, CR2, and CR3. Upon optical immunohistochemical examination of frozen sections from human reactive lymph nodes and tonsils by a three-step immunoperoxidase technique, a strong staining of cell bodies and cytoplasmic extensions of FDC was observed in germinal centers with anti-CR1 and anti-CR2 antibodies. Staining for these antigens was also found on cytoplasmic extensions of FDC in the mantle zone and on the plasma membrane of B cells in the entire follicles. Staining of FDC with anti-CR2 antibody was more intense than that of B lymphocytes. Monoclonal antibodies directed against epitopes of the alpha-chain of CR3 weakly stained FDC in follicles in a similar pattern to that which was observed on adjacent sections with mouse monoclonal antibody KIM4 that only recognizes FDC in human lymph nodes. Immunoelectron-microscopy was performed on frozen sections of a lymph node involved with a centroblastic centrocytic B malignant lymphoma and a reactive tonsil with the use of rabbit F(ab')2 anti-CR1 antibodies and mouse monoclonal anti-CR2 antibody. All the plasma membrane of the cell body and cytoplasmic extensions of FDC in germinal centers and in the mantle zones homogeneously stained for CR1 and CR2 antigens. Fibroblastic reticulum cells were negative. The plasma membrane of tumoral B lymphocytes strongly stained with anti-CR1 and weakly stained with anti-CR2 antibodies. The presence of CR1, CR2, and CR3 on FDC is a unique surface characteristic of these cells that should optimally allow the cells to bind antigen/antibody complexes bearing any type of C3 fragment.     

The postnatal development of cell populations in the rat popliteal lymph node

Summary The postnatal development of the various cell populations in the rat popliteal lymph node was investigated applying enzyme-histochemical and immunohistochemical techniques. From birth, T-lymphocytes and interdigitating cells were demonstrable. During the development of the young lymph node, T-lymphocytes of the helper phenotype outnumbered the T-cells with a suppressor phenotype; they account for approximately 70% and 30% of all T-lymphocytes, respectively. At the very first day of postnatal life, post-capillary venules were already present. B-lymphocytes occurred later than T-cells during ontogeny; they were found on the second day after birth, most of them being IgM- or IgG-bearing lymphocytes. The first primary follicles occurred at day 18 and contained principally membrane-stained IgM cells and, to a lesser extent, membrane-stained IgG cells. The appearance of follicular dendritic cells correlated with the formation of primary follicles. With respect to the macrophages, it appeared that the ED1- and ED3-positive subpopulations were present with a similar distributional pattern as seen in adults, but in considerably lower numbers. The expression of ED2, however, showed a sudden increase in the third week of life. Findings of the present study are discussed in relation to those obtained in other investigations dealing with the ontogenetic development of lymphoid organs.Abbreviations IDC interdigitating cell - cIg cytoplasmic immunoglobulin - sIg surface immunoglobulin - FDC follicular dendritic cell - PBS phosphate-buffered saline - PCV post-capillary venule - PLN popliteal lymph node     

Correlation of N-myc downstream-regulated gene 1 subcellular localization and lymph node metastases of colorectal neoplasms

In colorectal neoplasms, N-myc downstream-regulated gene 1 (NDRG1) is a primarily cytoplasmic protein, but it is also expressed on the cell membrane and in the nucleus. NDRG1 is involved in various stages of tumor development in colorectal cancer, and it is possible that the different subcellular localizations may determine the function of NDRG1 protein. Here, we attempt to clarify the characteristics of NDRG1 protein subcellular localization during the progression of colorectal cancer. We examined NDRG1 expression in 49 colorectal cancer patients in cancerous, non-cancerous, and corresponding lymph node tissues. Cytoplasmic and membrane NDRG1 expression was higher in the lymph nodes with metastases than in those without metastases (P < 0.01). Nuclear NDRG1 expression in colorectal neoplasms was significantly higher than in the normal colorectal mucosa, and yet the normal colorectal mucosa showed no nuclear expression. Furthermore, our results showed higher cytoplasmic NDRG1 expression was better for differentiation, and higher membrane NDRG1 expression resulted in a greater possibility of lymph node metastasis. These data indicate that a certain relationship between the cytoplasmic and membrane expression of NDRG1 in lymph nodes exists with lymph node metastasis. NDRG1 expression may translocate from the membrane of the colorectal cancer cells to the nucleus, where it is involved in lymph node metastasis. Combination analysis of NDRG1 subcellular expression and clinical variables will help predict the incidence of lymph node metastasis.     

Fine-needle aspiration of mucin-producing thyroid tumors

Objective: Mucin-producing thyroid tumors are extremely rare. Nonetheless, we have encountered three such cases in fine-needle aspiration. We report the cytologic and histologic findings and review the literature. Study Design: Cytologic features were studied on direct smears using Romanovsky stain to detect background substance and Papanicolaou stain to analyze nuclear and cytoplasmic features. The cytologic features were correlated with histology. Mucin was demonstrated by mucicarmine, Alcian Blue/PAS, and Alcian Blue (pH 2.5). Results: The cytologic features related to mucin include: (1) thick luminal mucin globules and signet ring cells aspirated from an 83-year-old woman with a 3-cm signet ring cell follicular adenoma, (2) abundant fluffy mucin containing signet ring cells in cohesive fragments aspirated from a 75-year-old man with the bilateral signet ring cell follicular variant of papillary carcinoma, which is the first case in the English literature, and (3) abundant thin mucoid mucin aspirated from the lymph node of an 86-year-old woman with a 5-cm mucinous poorly differentiated thyroid carcinoma. Conclusion: The occurrence of mucin in thyroid fine-needle aspiration does not necessarily indicate metastasis, and the presence of mucin in cervical lymph nodes does not exclude the thyroid gland as a possible primary.     

Development and cell phenotypes in primary follicles of foetal sheep lymph nodes

Lymph nodes from sheep foetuses and postnatal lambs were examined to determine the participation of different leucocyte populations in primary follicle formation, with special emphasis on the emergence and subsequent development of follicular dendritic cells during late gestation and early postnatal life. A series of immune and enzyme histochemical markers was used. The first 5′-nucleotidase-positive primary follicles were found at 80 days gestational age (gestation in sheep is 150 days) in superficial cervical lymph nodes. In the last month of gestation the primary follicles possessed follicular dendritic cells, macrophages, dendritic cells, and CD5-positive lymphocytes, in addition to IgM-positive cells. Follicular dendritic cells in primary follicles were found to be ultrastructurally immature. These follicular dendritic cells were characterised by a few, coarse surface projections and many ribosomes attached to the endoplasmic reticulum. A final differentiation to mature follicular dendritic cells was coincident with the postnatal germinal centre reaction. Computer-assisted morphometric analysis demonstrated that the size of 5′-nucleotidase-positive primary follicles in the distal jejunal lymph node, but not in the superficial cervical lymph node, increased significantly during late gestation. It was concluded that stromal cells in primary follicles of foetal sheep lymph nodes were a continuously developing population but that ultrastructural maturity was only achieved in the germinal centres of postnatal lambs.     

Expression of CD44 and cyclin D1 in fine needle aspiration cytology of papillary thyroid carcinoma

OBJECTIVE: To compare the expression pattern of CD44 and cyclin D1 immunostaining in fine needle aspiration specimens of papillary carcinoma of the thyroid and nonpapillary lesions. STUDY DESIGN: The study was performed on 80 fine needle aspiration cytologic smears of thyroid lesion retrospectively using monoclonal antibodies and on histologic material from a proportion of cases. RESULTS: Most papillary carcinomas expressed intense cell membrane or diffuse cytoplasmic staining for CD44 (97.8%). Focal immunoreactivity was observed in follicular neoplasms (28.5%) and nodular goiter (4.7%). There was no difference in CD44 immunostaining between follicular carcinoma and adenoma. Cyclin D1 was expressed in the nuclei of most papillary carcinomas (79.2%). Focal nuclear immunoreactivity was noted in nodular goiters (23.5%) and follicular neoplasms (10%). In resected specimens, all papillary carcinomas (19 cases) showed intense membranous or granular CD44 immunoreactivity. Focal cyclin D1 expression was noted in 52.6%. There was no difference in CD44 and cyclin D1 expression between the group of papillary carcinomas with regional lymph node metastasis as compared to those without metastasis. Positive staining for both CD44 and cyclin D1 would strongly favor papillary carcinoma, although further studies on cytologic material are necessary to verify this diagnostic approach. CONCLUSION: Most papillary carcinomas express CD44 and cyclin D1, whereas it is less common in follicular neoplasms and nodular goiter. This may be helpful in diagnostically difficult cases.     

Enzyme and immunohistochemistry of follicular hyperplasia in AIDS-related lymphadenopathy

We used a panel of monoclonal and polyclonal antibodies to analyze frozen and paraffin-embedded lymph node biopsy specimens from 25 intravenous drug abusers (IVDA) with acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy histologically characterized by follicular hyperplasia. Our aim was to obtain diagnostic clues to this commonly occurring pattern. Double-labelling immunohistological studies were also performed on selected frozen sections and 13 plastic-embedded specimens were tested by a number of enzyme reactions. Consistent features in IVDA included abnormally high numbers of intrafollicular T-cells, positive for acid phosphatase and beta-glucuronidase, most of which had Leu-2a-positive phenotype; a marked reduction or loss of mantle zone B-cells (positive for surface IgD-IgM and alkaline phosphatase); and disarray of the network of follicular dendritic reticulum cells (DRCs), as revealed with DRC-1 and anti-S-100 protein antibodies or with reaction for 5'-nucleotidase. When present, distinctive intrafollicular clusters of Leu-2a-positive T-cells and mantle zone B-cells were nearly always associated with areas lacking DRCs in some patients. The intrafollicular hypervascularity invariably found in IVDA proved to be of a true capillary nature, as demonstrated by alkaline phosphatase, 5'-nucleotidase, and ATPase reactions. In control tissues, all showing absence of Leu-2a-positive intrafollicular T-cells, most of the above individual changes could be detected, although they were occasional, mild, and never associated within the same follicle. By contrast, combined immunohistological and enzyme histochemical findings in IVDA indicated that in most follicles such changes were marked and very often associated within the same follicle in each case.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical relevance of peripheral blood lymphocyte morphology and lymph node histology in chronic lymphocytic leukemia

Peripheral blood lymphocyte (PBL) morphology and lymph node (LN) histology were evaluated in a prognostic study conducted in 247 patients with low-grade malignancies of B lymphocytes. The patients were classified according to total tumor mass (TTM) distribution pattern. A simple classification based on quantification of lymphoid cells that were morphologically different from small lymphocytes of peripheral blood was evaluated in the 166 leukemic patients. The lymph node histology was studied in 211 patients who had lymph node enlargement. The pattern of growth (pseudofollicular, diffuse, and tumorous), the proportion of distinct lymphocytes, and the degree of capsule infiltration were evaluated in 130 patients who showed leukemic involvement as well as enlargement of lymph nodes and/or spleen. Both PBL and LN morphologies correlate with the TTM distribution pattern and demonstrate a prognostic value that is independent of clinical characteristics. From the PBL morphology the LN morphology can be predicted. The prognostic power of the PBL morphology is lost after adjustment for the pattern of growth in LN and vice versa. A significant overlap between the PBL morphology and LN histology suggests some independence between the two variables and points to the possibility of biased classification if only one of the compartments is evaluated. Capsular infiltration is, however, a prognostic factor independent of both clinical and morphological characteristics. Morphological analysis in CLL is clinically relevant. Precise classification of patients requires analysis of both PBL and LN morphology to ensure comparability of patients admitted to clinical trials.     

A study of lymphocyte subsets in human normal tonsil and lymph node

A series of T and B lymphocyte specific monoclonal antibodies was used to determine the localization of lymphocyte subpopulation in frozen and paraffin tissue sections of human normal tonsil and lymph node by means of immunocytochemical technique. In the paracortical and interfollicular area of tonsil and lymph node, most lymphocytes reacted with Leu 1, Leu 3 a, Leu 4 and OKT4. The numbers of Leu 2 a and OKT8 positive cells were rare in tissue. These cells were not only limited in paracortical area, they also appeared in considerable numbers in medullary cords of lymph nodes. Leu 2 a and OKT 8 positive cells decreased with prominent follicular hyperplasia of tonsils. In addition, substantial leu 3 a and Leu 4 cells were found in the germinal centers. This finding supports the importance of these lymphocyte subsets in regulation of human immune response. In the mantle zone of secondary follicles, the majority of lymphocytes were positive for OKB 2 and BA 1, whereas, the IgM positive cells were predominately observed in the cytoplasma and extracellular substance of B lymphocytes in the germinal centers, but the lymphocytes bearing sIgM were rarely observed. In the mantle zone, the IgM were frequently found on the surface of membrane of small lymphocytes, however, the staining intensity was much than that in the germinal centers.     

Increased Expression of Flotillin-2 Protein as a Novel Biomarker for Lymph Node Metastasis in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. Flotillin-2 (Flot-2) is not only an important component of cellular membrane, but also involves in various cellular processes such as membrane trafficking, T cell and B cell activation, regulation of several signaling pathways associated with cell growth and malignant transformation, keeping structure and junction of epidermal cells and formation of filopodia. Although such molecular effects of Flot-2 have been reported, whether the expression of Flot-2 protein is associated with clinicopathologic implication for NPC has not been reported. The purpose of this research is to investigate the expression of Flot-2 protein in NPC and control nasopharyngeal epithelial tissues by immunohistochemistry and elucidate the association between the expression of Flot-2 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of Flot-2 expression in the NPC, nasopharyngeal epithelia with atypical hyperplasia and in the control nasopharyngeal mucosa epithelia was 88.8% (119/134), 76.9% (10/13) and 5.7% (5/88), respectively. There was significantly higher expression of Flot-2 protein in NPC and nasopharyngeal epithelia with atypical hyperplasia compared to the control nasopharyngeal mucosa epithelia (P<0.001, respectively). The positive percentage of Flot-2 protein expression in NPC patients with lymph node metastasis was significantly higher than those without lymph node metastasis. Increasing of Flot-2 expression was obviously correlated with clinical stages of NPC patients. The expression of Flot-2 was proved to be the independent predicted factor for lymph node metastasis by multivariate analysis. The sensitivity of Flot-2 for predicting lymph node metastasis of NPC patients was 93%. Taken together, our results suggest that the increased expression of Flot-2 protein is a novel higher sensitivity biomarker that can predict lymph node metastases in NPC.     

Development and cell phenotypes in primary follicles of foetal sheep lymph nodes

Lymph nodes from sheep foetuses and postnatal lambs were examined to determine the participation of different leucocyte populations in primary follicle formation, with special emphasis on the emergence and subsequent development of follicular dendritic cells during late gestation and early postnatal life. A series of immune and enzyme histochemical markers was used. The first 5-nucleotidase-positive primary follicles were found at 80 days gestational age (gestation in sheep is 150 days) in superficial cervical lymph nodes. In the last month of gestation the primary follicles possessed follicular dendritic cells, macrophages, dendritic cells, and CD5-positive lymphocytes, in addition to IgM-positive cells. Follicular dendritic cells in primary follicles were found to be ultrastructurally immature. These follicular dendritic cells were characterised by a few, coarse surface projections and many ribosomes attached to the endoplasmic reticulum. A final differentiation to mature follicular dendritic cells was coincident with the postnatal germinal centre reaction. Computer-assisted morphometric analysis demonstrated that the size of 5-nucleotidase-positive primary follicles in the distal jejunal lymph node, but not in the superficial cervical lymph node, increased significantly during late gestation. It was concluded that stromal cells in primary follicles of foetal sheep lymph nodes were a continuously developing population but that ultrastructural maturity was only achieved in the germinal centres of postnatal lambs.     

Experimental allergic encephalomyelitis: changes in growth and proliferation within the draining lymph node following injection of basic encephalitogenic protein in Freund's complete adjuvant

Changes in wet weight, dry mass, and DNA synthesis of draining lymph nodes from rats injected with encephalitogenic basic protein in Freund's complete adjuvant (FCA) were studied. Lymph nodes of rats injected with encephalitogenic basic protein in FCA show accelerated enlargement from the second up to the fourth day after injection, as compared to lymph nodes of rats injected with FCA alone, or with nonencephalitogenic basic protein in FCA. The greatest difference in lymph node weight was found on the fourth day. At this time cell division is higher in the group injected with encephalitogenic protein in FCA than in the group injected with FCA alone. However, the increased division of cells in situ cannot account, in and by itself, for the enlargement of the lymph node which was observed. It is concluded that migration of lymphocytes into the lymph node makes a substantial contribution to the hyperplasia of the lymph node.The results suggest that accelerated lymph node enlargement may be specific, at least in part, for induction of experimental allergic encephalomyelitis.     

Proteomic identification of new biomarkers and application in thyroid cytology

OBJECTIVE: To validate proteins identified by proteomics as potentially usable markers in thyroid pathology. STUDY DESIGN: Frozen sections of thyroid tumors were manually micro-dissected and proteins extracted. Two-dimensional (2D) gel electrophoresis and subsequent liquid chromatography/mass spectroscopy were performed, and differentially expressed proteins were identified. Validation of candidates for tumor markers (galectin-1, galectin-3, S100C and voltage-dependent anion channel 1 [VDAC1]) was done by immunohistochemistry in 21 cell blocks from fine needle aspiration biopsies (FNAB) and corresponding histology specimens (13 cases). RESULTS: Galectin-3 was negative in benign lesions and positive in FNAB from papillary carcinoma (5 of 5), follicular variant of papillary carcinoma (1 of 4) and follicular carcinoma (1 of 2). S100C was positive in some benign lesions: hyperplasia (2 of 4), goiter (1 of 3) and follicular adenoma (1 of 3), with predominantly nuclear pattern of staining. S100C was positive in malignant lesions, showing cytoplasmic location. Galectin-1 was negative in benign lesions and positive in follicular carcinoma (1 of 2), papillary carcinoma (2 of 5) and follicular variant of papillary carcinoma (1 of 4). VDAC1 was detected in benign and malignant lesions, showing a strong positivity in follicular carcinomas. CONCLUSION: Immunohistochemical validation of potential markers is a crucial step before clinical application in diagnosis. Galectin-3, galectin-1 and S100C can be used to help in discriminating benign and malignant thyroid lesions.     

Melatonin protects against experimental immune ovarian failure in mice

Experimental immune ovarian failure induced in CBA mice by either administration of xenogenic anti-ovarian antibodies or immunization with allogenic ovarian extracts impaired the meiotic maturation of oocytes and increased apoptosis of follicular cells. Immunization was accompanied with the inflammation and active immune reaction, as shown by the enlargement of regional lymph nodes, the increase of apoptosis in cultured lymph node cells and the increase of band and segmented neutrophil percentage in the blood. Triple injections of melatonin (5 mg/kg of the body weight) an hour before antibodies administration restored the meiotic maturation of oocytes and supported the survival of follicular and lymph node cells. In contrast, melatonin application upon immunization was not effective to prevent the ovary impairment and cell death. It is concluded that melatonin protects against immune ovary failure induced by xenogenic anti-ovarian antibodies.     

Patterns of Lymph Node Pathology; Fine Needle Aspiration Biopsy as an Evaluation Tool for Lymphadenopathy: A Retrospective Descriptive Study Conducted at the Largest Hospital in Africa

Background

Lymphadenopathy is a common clinical presentation of disease in South Africa (SA), particularly in the era of Human Immunodeficiency Virus (HIV) and tuberculosis (TB) co-infection.

Methods

Data from 560 lymph node biopsy reports of specimens from patients older than 12 years at Chris Hani Baragwanath Academic Hospital (CHBAH) between 1 January 2010 and 31 December 2012 was extracted from the National Health Laboratory Service (NHLS), division of Anatomical Pathology. Cytology reports of lymph node fine needle aspirates (FNAs) performed prior to lymph node biopsy in 203 patients were also extracted from the NHLS. Consent was not obtained from participants for their records to be used as patient information was anonymized and de-identified prior to analysis.

Results

The majority of patients were female (55%) and of the African/black racial group (90%). The median age of patients was 40 years (range12–94). The most common indication for biopsy was an uncertain diagnosis (more than two differential diagnoses entertained), followed by a suspicion for lymphoma, carcinoma and TB. Overall, malignancy constituted the largest biopsy pathology group (39%), with 36% of this group being carcinoma and 27% non-Hodgkin lymphoma. 22% of the total sampled nodes displayed necrotizing granulomatous inflammation (including histopathology and cytology demonstrating definite, and suspicious for mycobacterial infection), 8% comprised HIV reactive nodes; in the remainder no specific pathology was identified (nonspecific reactive lymphoid hyperplasia). Kaposi sarcoma (KS) accounted for 2.5% of lymph node pathology in this sample. Concomitant lymph node pathology was diagnosed in four cases of nodal KS (29% of the subset). The co-existing pathologies were TB and Castleman disease. HIV positive patients constituted 49% of this study sample and the majority (64%) of this subset had CD4 counts less than 350 cells/ul. 27% were HIV negative and in the remaining nodes, the HIV status of patients was unknown. The most common lymph node pathologies in HIV positive patients were Mycobacterial infection (31%), HIV reactive nodes (15%), non-Hodgkin lymphoma (15%) and nonspecific reactive lymphoid hyperplasia (15%). Only 8.7% were of Hodgkin lymphoma. In contrast, the most common lymph node pathologies in HIV negative patients were nonspecific reactive lymphoid hyperplasia (45%), carcinoma (25%) and Mycobacterial infection (11%). In this group, non-Hodgkin lymphoma and Hodgkin lymphoma constituted 9% and 8%, respectively. There were more cases of high-grade non-Hodgkin lymphoma in the HIV positive group compared to the HIV negative group. FNA and lymph node biopsy had statistically significant good agreement with regard to Hodgkin lymphoma (K 0.774, SE 0.07, 95% CI 0.606-0.882, p=0.001), non-Hodgkin lymphoma (K 0.640, SE 0.07, 95% CI 0.472-0.807, p=0.001), carcinoma (K 0.723, SE 0.069, 95% CI 0.528-0.918, p=0.001), and mycobacterial infection (K 0.726, SE 0.07, 95% CI 0.618-0.833, p=0.001).

Conclusions

The most common lymph node pathologies in CHBAH are malignancies, nonspecific reactive lymphoid hyperplasia, necrotizing granulomatous inflammation and HIV reactive nodes. The distribution of disease differs in HIV positive patients. Overall, adequate FNA samples of lymph nodes have been found to have good correlation with lymph node biopsy findings in our setting.