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Scrofula revisited: an update on the diagnosis and management of tuberculosis of superficial lymph nodes.

Lymph node tuberculosis is a disease of great antiquity. It is the commonest form of extra-pulmonary tuberculosis, and is probably the commonest cause of chronic lymphadenitis in children. Even after the advent of effective chemotherapy for tuberculosis, it still poses considerable problems in diagnosis and management. The disease usually presents as a painless lymphadenopathy of the superficial lymph nodes of insidious onset, which may proceed to abscess and sinus formation if neglected. Cervical nodes are most commonly affected, but multiple node involvement is common. Differential diagnosis include other infections, neoplasia, congenital conditions in the head and neck and rarely, drug reactions. Diagnosis, whenever feasible, should be made on the basis of histological evidence after lymph node biopsy. Diagnosis made on clinical grounds has poor specificity and will result in a great degree of over diagnosis. Recently, the role of fine needle aspiration cytology as an initial screening procedure has been recognized. The Tuberculosis Research Centre carried out the first clinical trial which established the efficacy of short course chemotherapy in the treatment of childhood lymph node tuberculosis. In 168 children with biopsy confirmed lymph node tuberculosis treated with an intermittent six month regimen, the cure rate after five years was 95%. The Revised National Tuberculosis Control Programme recommends that patients with lymph node tuberculosis (Category 3) should be treated with rifampicin and isoniazid three times a week for six months, with pyrazinamide for the first two months.

Antitubercular Agents↗

Normal structure, function, and histology of lymph nodes.

Lymph nodes are traditionally regarded as having three compartments, the cortex, paracortex and medulla. B and T cells home to separate areas within these compartments, interact with antigen presenting cells, and undergo clonal expansion. This paper provides structural and functional details about how the lymph node brings lymphocytes and antigen presenting cells together. The concept of the lymphoid lobule as the basic functional and anatomic unit of the lymph node is developed and utilized to provide a framework for understanding lymph node pathobiology. Understanding the histomorphologic features of the lymphoid lobule and the role of the reticular meshwork scaffolding of the lymph node and how these related to the cortex, paracortex and medulla provides a unique approach to understanding lymph node structure and function.

Animals↗

Detection and relevance of immunohistochemically identifiable tumor cells in lymph nodes.

Lymph node metastasis is a well-known feature of poor prognosis in potentially resectable solid epithelial tumors. However, a significant number of apparently lymph node negative patients die early of metastatic disease. Therefore, it has to be assumed that in some patients an early tumor cell dissemination has occurred which is clearly underestimated by current staging procedures. Recently, it has been shown, that an early dissemination of individual carcinoma cells to regional lymph nodes can be detected by using sensitive immunocytochemical techniques with monoclonal antibodies against epithelium-specific proteins. The incidence of immunohistochemically positive patients varies between 12% and 70% depending on the type of primary tumor, the immunohistochemical staining procedure used, and especially on the primary monoclonal antibody. The detection of disseminated tumor cells in lymph nodes by immunocytochemistry is associated with a poorer prognosis in different types of epithelial tumors such as lung cancer or esophageal cancer. The immunocytochemical method might also be useful in the detection of occult tumor cells in sentinel lymph nodes. In conclusion, the immunohistochemical detection of disseminated tumor cells in lymph nodes can help to obtain a more exact identification of patients with an unfavorable prognosis. Whether the identified patients will gain from an adjuvant therapy has to be evaluated in further studies.

Biomarkers, Tumor↗

Ischaemic changes in human mesenteric lymph nodes.

Lymph node lesions attributable to ischaemia are described in the mesenteric nodes from 10 patients with volvulus of the small and large bowel. Frank infarction, the microanatomy of which differs from that seen in superficial lymph nodes, is one of the nodal lesions evoked by ischaemia. Two others in the form of lymphocyte depletion and capsular hypervascularity also appear to result from vascular occlusion. These three lesions were also found in nodes associated with 'primary' venous and arterial infarction of the bowel mucosa, but not in non-vascular diseases of the small bowel or colon. The enhanced frequency of infarction in volvulus with mucosal necrosis, as opposed to cases with 'primary' vascular thromboses suggest that ischaemic lymph node changes are more frequent when several sets of vessels are occluded. Distension of lymph node sinuses, erythrocyte extravasation, and dilatation of small intranodal vessels were not restricted to vascular cases, and appear to be less specific reactions to ischaemia. The range of ischaemia-induced reactions is wider than has hitherto been recognized in human lymph nodes.

Adult↗

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, course 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.

5'-Nucleotidase↗

Passive seeding in metanephric adenoma: a review of pseudometastatic lesions in perinephric lymph nodes.

Lymph node involvement derived from a discrete neoplastic process fundamentally implies tumor malignancy. However, rarely, inconsequential passive transport of benign neoplastic cells to the lymph node can occur and may cause confusion as to the nature of the neoplasm (ie, malignant vs benign). We describe a 10-cm right renal metanephric adenoma incidentally discovered in a 30-year-old woman during cesarean section for a triplet pregnancy. Subsequent nephrectomy following an equivocal needle biopsy diagnosis showed histologic features classic for metanephric adenoma, including the lack of cytologic atypia and mitoses. Necrosis present in this lesion appeared to be secondary to tumor physical disruption. The tumor cells were positive for Wilms tumor 1 (WT1) antigen, pankeratin, and CD57, focally positive for epithelial membrane antigen, and negative for cytokeratin 7, cytokeratin 34betaE12, and CD56. Electron microscopy confirmed the tumor's epithelial nature, and cytogenetics revealed a diploid 46XX karyotype. The tumor proliferation index with Ki-67 was only 3% to 5% and the proliferating cell nuclear antigen index was 0%. A single, concurrently resected hilar lymph node contained scattered subcapsular, sinusoidal, and focally intralymphovascular psammoma bodies along with occasional adherent epithelial cells. These cells were highlighted by pankeratin but were nonreactive to WT1 antigen, similar to the nonviable cells in the primary tumor. Clinical surveillance and follow-up showed no disease recurrence 4 years after nephrectomy. We postulate that the lymph node inclusions found in this case represent passive transport of neoplastic cells to the lymph node following manipulation of the renal mass. We conclude that this phenomenon is understudied and underrecognized and can easily be mistaken for metastasis.

Adenoma↗

Histopathologic and immunohistochemical characterization of a primary papillary thyroid carcinoma in the lateral cervical lymph node.

Lymph nodes in the neck are known to occasionally contain benign epithelial inclusions and can be rare primary site of various tumors usually occurring in other organs. Papillary thyroid carcinoma in the lateral neck lymph node with co-existing ectopic thyroid inclusions has not been reported previously. A 41-year-old male patient, who had normal thyroid function and no history of neck irradiation, was seen with a slowly enlarging mass in the right lateral neck. At surgery the cervical mass was found to be separate from the thyroid proper without any attachments in between. Papillary thyroid carcinoma and co-existing thyroid inclusions were identified within the lateral cervical lymph node. Immunohistochemistry detected strong and diffuse cytoplasmic positivity with antibodies against CK19 and CK903 in papillary thyroid carcinoma. Benign thyroid follicles within the lymph node were only weakly and focally stained. Thorough examination confirmed no malignancy in the total thyroidectomy specimen. Furthermore, small foci of metastatic papillary carcinoma were identified in two ipsilateral lymph nodes from neck dissection specimen. These findings suggest development of primary papillary thyroid carcinoma from malignant transformation of benign intranodal thyroid inclusions.

Adult↗

[Cancer and the lymph nodes].

Lymph node metastasis of cancer has great significance with respect to its circumstances, diagnosis, treatment and prognosis. In recent years, especially, we have experienced advances in the field of lymphatic circulation and the role played by lymph nodes in immunological surveillance. The various associated problems and the progress which has been made with regard to cancer and lymph nodes are discussed.

Aging↗

Histopathology of the lymph nodes.

Lymph nodes function as filters of tissues and tissue fluids and are sites of origin and production of lymphocytes for normal physiological functions. As part of this normal function, they react to both endogenous and exogenous substances with a variety of specific morphological and functional responses. Lesions can be both proliferative and nonproliferative, and can be treatment-related or not. The histological evaluation of lymph nodes is necessary in order to understand the immunotoxic effects of chemicals with the resulting data providing an important component of human risk assessment. It is the challenge of the toxicologic pathologist to interpret the pathology data within the complete clinical evaluation of the entire animal. Daily insults, ageing and toxins can alter the normal histology and primary function of lymph nodes. Therefore it is important to distinguish and differentiate lesions that occur naturally during normal development and ageing from those that are induced by xenobiotics. To achieve this goal, comparison with strain- age- and sex-matched controls is crucial.

Animals↗

Characteristics and in vivo homing of long-term T-cell lines and clones derived from tumor-draining lymph nodes.

Lymph nodes draining a progressively growing tumor contain T-cells which can be activated sequentially by anti-CD3 and IL-2 to differentiate into tumor-specific effector cells. In this study, long-term cultured T-cell lines were established from activated MCA 106 tumor-draining lymph node cells by periodic stimulation with irradiated tumor cells in the presence of low concentrations of IL-2 (< or = 60 International units/ml). Such long-term cultured cell lines maintained therapeutic effects when transferred to tumor-bearing mice. Although the initial anti-CD3/IL-2-activated T-cells displayed a broad distribution of T-cell antigen receptor beta chain variable region (V beta) usages, long-term cultured cells were dominated by T-cells expressing a few V beta elements. Of six cell lines, only three V beta phenotypes (V beta 5, 11, 13) were identified, and individual cell lines frequently expressed a single V beta gene product. Despite restricted V beta expression, each cell line mediated tumor-specific reactivity in adoptive immunotherapy. Many T-cell clones were isolated from long-term cell lines. Three V beta 13 T-cell clones demonstrated specific in vivo antitumor effects, whereas two V beta 11 and two V beta 5 clones revealed a significant degree of cross-reactivity against the antigenically distinct MCA 205 tumor. Although the initial anti-CD3/IL-2-activated cells lacked demonstrable cytotoxic reactivity, T-cell clones derived from them exhibited cytotoxic effects to the MCA 106 tumor cells. The specificity of the cytotoxicity mediated by each clone reflected its in vivo antitumor effects. Furthermore, studies of in vivo localization of cloned T-cells demonstrated tumor-specific infiltration of the 5A2 (V beta 13) clone to the MCA 106 tumor metastases, whereas clone 9H6 (V beta 5) revealed some accumulation in the MCA 205 tumor. Again, the in vivo antitumor effects of the 9H6 clone correlated with its in vivo infiltration into the specific MCA 106 and the nonspecific MCA 205 metastases. Taken together, the long-term culture of anti-CD3/IL-2-activated tumor-draining lymph node cells resulted in selective expansion of a few T-cells as evidenced by the limited T-cell receptor V beta expression. Our results also demonstrated that systemically administered antitumor T-cell clones gained access and accumulated at metastatic tumor sites, and the degree of infiltration correlated with the specificity of the in vivo antitumor effect as well as the in vitro cytotoxic activity.

Animals↗

A three-dimensional reconstruction of metastatic adenocarcinoma in lymph node.

Lymph nodes are a common site of metastatic cancer. The ability to view the three-dimensional configuration of complex biological structures, rendered in solid model form, might help to further elucidate the pathophysiology of metastatic disease. This paper presents a method for three-dimensional reconstruction from serial sections of a lymph node containing metastatic adenocarcinoma. The reconstruction and subsequent animation were carried out using the P3D graphics software (developed at the Pittsburgh Supercomputing Center) and rendered by the Dore high-speed renderer on an Ardent Titan graphics workstation. As different views of the model were produced, they were recorded a frame at a time on U-matic video tape. A three-dimensional solid-modeled object portrays metastatic, neoplastic elements within a lymph node.

Adenocarcinoma↗

DIAGNOSTIC PROBLEMS IN BILIARY DUCT LYMPH NODES.

Lymph nodes in the area of the cystic duct are sometimes included with surgically removed gall bladders for pathological examination. These nodes may show a range of histological changes, including sinus histiocytosis and panhyperplasia with, or without giant cell systems, granuloma and fibrosis. The nature and incidence of these changes were studied with appropriate lymph nodes collected routinely from 80 patients, mainly at necropsy. Awareness of these changes should obviate possible serious error in histological diagnosis.

Cystic Duct↗

Benign lymph node hyperplasia and lymph node metastases in rabbits. Animal models for magnetic resonance lymphography.

OBJECTIVES: Experimental models of reactive lymph-node hyperplasia and lymph-node metastasis were developed for magnetic resonance imaging (MRI). METHODS: Reactive lymph-node hyperplasia was induced in 20 rabbits by injection of an egg-yolk emulsion intramuscularly in the hind limbs and subcutaneously in the flanks. In another 20 rabbits, lymph-node metastasis was induced by implantation of a squamous cell carcinoma (VX2 tumor) in one hind limb. Five rabbits remained untreated. Signal intensity and size of iliac medical and popliteal lymph nodes were investigated with T1-, T2-, and proton-density-weighted spin-echo sequences at 1.5 T. In addition, lymph-node activity and metastatic involvement were assessed histologically. RESULTS: Lymph nodes in untreated animals were small and difficult to visualize by MRI. After egg-yolk-induced reactive lymph-node hyperplasia, the enlarged nodes were well demonstrated by MRI. Implantation of VX2 tumors led to different degrees of lymph-node metastasis (micrometastasis, partial and complete metastatic permeation), depending on growth period and size of the primary tumor. In MR images, lymph nodes of untreated, stimulated, and tumor-bearing rabbits were not differentiable by signal intensity. CONCLUSION: Reactive lymph-node hyperplasia induced by interstitial egg-yolk injection and lymph-node metastasis secondary to implantation of VX2 tumors cannot be differentiated by standard MRI. Therefore, these models may serve for testing the efficacy of lymphographic techniques in MRI.

Animals↗

Renal cell carcinoma with retroperitoneal lymph nodes: role of lymph node dissection.

PURPOSE: We better defined the benefits and morbidity of lymph node dissection in patients with localized renal cell carcinoma using the experience of patients treated at our institution. MATERIALS AND METHODS: A retrospective cohort study was performed with outcome assessment based on the chart review of demographic, clinical and pathological data in 1,087 patients with renal cell carcinoma treated at our institution. Patients with renal cell carcinoma who did not undergo nephrectomy as part of cancer treatment, those with bilateral disease and those for whom nodal status was unknown were not included in this study. A total of 900 patients meeting these criteria who underwent nephrectomy for unilateral renal cell carcinoma at our medical center form the principal study population. RESULTS: Positive lymph nodes were associated with larger, higher grade, locally advanced primary tumors that were more commonly associated with sarcomatoid features. Positive nodes were 3 to 4 times more common in patients with metastatic disease and the majority of these patients could be identified preoperatively. The survival of patients with regional lymph node involvement only was identical to that of patients with distant metastatic disease only. Patients with regional nodes and distant metastases had significantly inferior survival to those with either condition alone. In node negative cases lymph node dissection can be performed with no additional morbidity but it confers no survival advantage. In node positive cases lymph node dissection can also be performed safely but it is associated with improved survival and a trend toward an improved response to immunotherapy. CONCLUSIONS: Regional lymph node dissection is unnecessary in patients with clinically negative lymph nodes since it offers extremely limited staging information and no benefit in terms of decreasing disease recurrence or improving survival. In patients with positive lymph nodes lymph node dissection is associated with improved survival when it is performed in carefully selected patients undergoing cytoreductive nephrectomy and postoperative immunotherapy. When lymph nodes are present, they should be resected when technically feasible.

Analysis of Variance↗