Detection of Epstein-Barr virus-associated antigen in fine needle aspiration smears from cervical lymph nodes in the diagnosis of nasopharyngeal carcinoma

Epstein-Barr virus (EBV) has consistently been shown to be associated with undifferentiated nasopharyngeal carcinoma, and an EBV-associated nuclear antigen (EBNA) has been detected in the cells of nasopharyngeal carcinoma. A study on the applicability of EBNA detection in fine needle aspiration (FNA) smears from cervical lymph nodes in the diagnosis of metastatic nasopharyngeal carcinoma was performed. All 11 cases (100%) with metastatic nasopharyngeal carcinoma showed EBNA-positive tumor cells, characterized by bright, granulated nuclear fluorescence. Three (50%) of six cases with other metastatic head and neck carcinomas also showed EBNA-positive tumor cells. These findings suggest that the presence of EBNA-positive tumor cells in FNA smears from cervical lymph nodes is not specific for metastatic nasopharyngeal carcinoma. On the other hand, a negative result in the presence of tumor cells may help to exclude it. A larger study is required to verify these preliminary findings.     

Fine needle aspiration of Langerhans cell histiocytosis of the lymph nodes. A report of six cases

BACKGROUND: Fine needle aspiration (FNA) diagnosis of Langerhans cell histiocytosis (LCH) of the lymph nodes has been described rarely. CASES: LCH was confined to the lymph nodes in six children. The FNA smears showed high cellularity composed of many isolated Langerhans cells (LCs) with nuclear grooves and intranuclear inclusions. Also seen were numerous eosinophils, lymphocytes, giant cells, dendriticlike cells, macrophages and Charcot-Leyden crystals in a background of eosinophilic granules. Immunohistochemical study revealed a positive reaction with S-100 protein. CONCLUSION: The presence of LCs with nuclear grooves, eosinophils, giant cells and a positive reaction with S-100 protein aided the diagnosis of LCH of the lymph nodes. Charcot-Leyden crystals, intranuclear inclusions and dendriticlike cells were seen in this study. These findings have not been reported before in lymph node FNA smears of LCH.     

Fine needle aspiration cytologic findings in a case of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman syndrome)

The clinical, fine needle aspiration (FNA) cytologic and histologic findings in a case of sinus histiocytosis with massive lymphadenopathy (SHML) in a five-year-old boy are presented. The FNA smears showed a proliferation of plasma cells, lymphoid cells and histiocytes demonstrating emperipolesis that is characteristic of this benign disorder; these cytologic findings were reported as a reactive lymphoid infiltrate with a high content of benign histiocytes. The diagnosis was made on a subsequent open biopsy performed on the persistent lymphadenopathy. The differential diagnosis of lymph nodes containing a prominent component of histiocytes is discussed.     

Subclassification of localized Leishmania lymphadenitis in fine needle aspiration smears

OBJECTIVE: To describe the cytologic findings of localized Leishmania lymphadenitis and discuss the differential diagnosis. STUDY DESIGN: The study group consisted of 133 cases. All of them were diagnosed by fine needle aspiration (FNA) study. The ages ranged between 3 and 80 years, 102 were male and 31 female. Seventy lymph nodes were excised. RESULTS: The FNA smears revealed a polymorphic population of cells composed of lymphocytes, histiocytes, giant cells, abnormal plasma cells and tingible body macrophages. Leishman-Donovan (LD) bodies were identified in all cases, but their number differed from case to case. Granulomas, dendritic cells, mast cells and lymphoglandular bodies were identified in a substantial number of cases. Depending upon the presence of characteristic cytologic findings, the cases were divided into five major groups: acute inflammation with giant cells, histiocytic granulomas, epithelioid cell granulomas, plasma cell type and mixed histioplasmacytic type. CONCLUSION: Leishmaniasis is an uncommon cause of cervical lymphadenitis but should be considered in the differential diagnosis of unexplained lymphadenopathy in endemic countries. Demonstration of LD bodies is necessary for the diagnosis of this self-limited condition, for which no treatment is required.     

Fine needle aspiration cytodiagnosis of nasopharyngeal carcinoma in cervical lymph nodes. A study of 40 cases

The cytologic features of fine needle aspiration (FNA) samples of 40 metastatic nasopharyngeal carcinomas in cervical lymph nodes were reviewed. FNA was performed with 21-gauge or 23-gauge needles; the FNA smears were stained with the Papanicolaou stain or with hematoxylin and eosin. Several typical cytologic features were noted. All cases showed the presence of clusters of cohesive tumor cells, most of which were undifferentiated. Medium-sized oval vesicular nuclei were present in 85% of the cases; all cases had prominent nucleoli. The cytoplasm was generally pale, with ill-defined boundaries in 87.5% of the cases. Mitoses were present in 75% of the cases. Mature lymphocytes were intermingled with tumor cells in all cases. The cytologic features correlated with the histologic features in surgical biopsies of the nasopharynx and lymph nodes. The results show that FNA of cervical lymph nodes can aid in the diagnosis of otherwise occult nasopharyngeal carcinoma and in detecting residual or recurrent nodal disease in patients with nasopharyngeal carcinoma who had undergone treatment.     

T-cell/histiocyte-rich diffuse large B-cell lymphoma. Report of a case diagnosed by fine needle aspiration biopsy with immunohistochemical and molecular pathologic correlation

BACKGROUND: T-cell-rich B-cell lymphoma (TCRBL) is a lymphoma of B-cell type associated with a prominent component of T cells (constituting > 50% of the cellular population). We report the first case of TCRBL diagnosed by fine needle aspiration (FNA). It was confirmed by subsequent lymph node excision biopsy. CASE: A 37-year-old woman presented with a short history of chest wall pain. Examination revealed induration, warmth and armorlike swelling of the right anterior chest wall, axilla and upper arm, with matted lymph nodes in the ipsilateral axilla and supraclavicular fossa. FNA showed a polymorphic, lymphoid aspirate, among which were many small lymphocytes, significant numbers of centroblastlike cells and a few markedly atypical lymphoid cells with convoluted nuclei. Histiocytes, freely lying karyorrhectic debris and mitotic figures were readily identified. Plasma cells, eosinophils and Reed-Sternberg cells were not seen. The cell block contained similar cells, with larger lymphoid cells scattered among smaller lymphocytes. Immunohistochemical studies showed that the larger cells were B cells. Molecular studies on the cell block confirmed an immunoglobulin gene rearrangement. CONCLUSION: TCRBL is a distinct type of lymphoma that can be accurately diagnosed by FNA.     

Cytologic diagnosis of reactive lymphadenopathy in fine needle aspiration biopsy specimens

Reactive or benign lymphadenopathies were cytologically diagnosed in the aspirates of 62 (23.5%) of 265 cases with enlarged lymph nodes of the head, neck or inguinal region subjected to fine needle aspiration (FNA) biopsy. The cytomorphologic features characteristic of reactive lymphadenopathy are described in detail; some of the cell patterns were suggestive of a specific disease process. The similarities of cells and cell patterns that may pose differential diagnostic problems with malignant lymphomas are pointed out. This study emphasizes the role of FNA cytology in the diagnosis of some benign conditions.     

Comparison of diagnostic results obtained by fine needle aspiration cytology and tru-cut or open biopsies

In seven cases fine needle aspiration (FNA) cytology provided a diagnosis of neoplasm when the Tru-Cut (TC) tissue biopsies (four cases) and open biopsies (three cases) were negative. The specimens consisted of two breast carcinomas, two metastatic neoplasms in the liver, one metastatic melanoma in inguinal lymph nodes, a retroperitoneal mass and a pelvic mass. In the two cases of mammary carcinoma, TC biopsies were negative and FNAs were diagnostic of carcinoma. TC biopsies in the two cases of questionable hepatic metastasis were negative, but FNAs demonstrated a malignant neoplasm. Open biopsy of a retroperitoneal mass failed to diagnose a neoplasm however, subsequent ultrasound-directed FNA demonstrated a neoplasm, possibly seminoma. FNA cytology of inguinal lymph nodes in one case was diagnostic of melanoma; open biopsy showed no neoplasm. Because of the FNA diagnosis, additional sections were made and the presence of melanoma was confirmed. This series demonstrates that FNA cytology should be considered the initial diagnostic procedure more often.     

Fine needle aspiration of follicular dendritic cell sarcoma in an HIV-positive man: a case report

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is an uncommon neoplasm occurring not only in lymph nodes but also in extranodal sites. Because of an increasing number of case reports, awareness of this tumor has grown. The nature of the disease and its relation to other diseases, treatment, prognosis and immunochemistry findings are being actively studied. So far, only a limited number of cytology cases describing the fine needle aspiration (FNA) biopsy findings of FDC sarcoma have been reported. CASE: A 47-year-old man had a history of hypertension and human immunodeficiency virus (HIV) infection treated with antiretroviral therapy. He developed a slowly growing, nontender right neck mass over the course of 3 years. FNA revealed sheets and thick syncytial clusters of bland cells with pale cytoplasm and indistinct cell borders, round to oval nuclei with fine or vesicular chromatin, and small nucleoli. The mass was subsequently excised. A diagnosis of FDC sarcoma was made based on the histologic appearance and the marker studies. Conclusion The diagnosis ofFDC sarcoma in FNA can be suspected if a pathologist is aware of its characteristic features. Research studies have demonstrated the presence of HIV-related FDC hyperplasia. It is likely that HIV infection may have played a role in tumor formation in this patient. (Acta     

Cytology and immunocytology of infectious mononucleosis in fine needle aspirates of lymph nodes

Two cases of infectious mononucleosis with atypical clinical presentations were initially diagnosed by fine needle aspiration (FNA) of lymph nodes and subsequently confirmed by serologic studies. The cytologic features that allowed recognition included a high percentage of cells with relatively abundant cytoplasm that stained pale to deep blue using a Giemsa-type stain. Many of the cells had plasmacytoid features. The cells ranged in size from small lymphocytes to large immunoblastic forms. Other features included mitotic figures and occasional binucleated forms. Immunologic studies showed a mixture of B and T cells, with many of the cells having a cytotoxic/suppressor phenotype. The features seem to be relatively characteristic and distinct from those of malignant processes that could be aspirated in lymph nodes. Recognition of infectious mononucleosis by FNA in these cases allowed for confirmation by serologic studies, thereby avoiding the need for an excisional biopsy. These cases show that FNA of lymph nodes may shed light on the nature of the process underlying the lymphadenopathy in selected cases of clinically atypical infectious mononucleosis.     

Activation, differentiation, and migration of naive virus-specific CD8+ T cells during pulmonary influenza virus infection

The low precursor frequency of individual virus-specific CD8(+) T cells in a naive host makes the early events of CD8(+) T cell activation, proliferation, and differentiation in response to viral infection a challenge to identify. We have therefore examined the response of naive CD8(+) T cells to pulmonary influenza virus infection with a murine adoptive transfer model using hemagglutinin-specific TCR transgenic CD8(+) T cells. Initial activation of CD8(+) T cells occurs during the first 3 days postinfection exclusively within the draining lymph nodes. Acquisition of CTL effector functions, including effector cytokine and granule-associated protease expression, occurs in the draining lymph nodes and differentially correlates with cell division. Division of activated CD8(+) T cells within the draining lymph nodes occurs in an asynchronous manner between days 3 and 4 postinfection. Despite the presence of Ag for several days within the draining lymph nodes, dividing T cells do not appear to maintain contact with residual Ag. After multiple cell divisions, CD8(+) T cells exit the draining lymph nodes and migrate to the infected lung. Activated CD8(+) T cells also disseminate throughout lymphoid tissue including the spleen and distal lymph nodes following their emigration from draining lymph nodes. These results demonstrate an important role for draining lymph nodes in orchestrating T cell responses during a local infection of a discrete organ to generate effector CD8(+) T cells capable of responding to infection and seeding peripheral lymphoid tissues.     

Lymph node examination by fine needle aspiration in patients with known or suspected malignancy

In a series of more than 2,500 fine needle aspirates from multiple body sites, over 200 were clinically identified as lymph nodes from patients with known or suspected malignancy. The material was obtained using the easily manipulated Aspir-Gun with a 21-gauge or 22-gauge needle and syringe. Of the 200 lymph node specimens, 100 (50%) were cytologically reported as positive for malignancy. Ninety cases had surgical pathology specimens available for comparison with the fine needle aspiration (FNA) specimens. For the 88 of these cases with satisfactory FNA specimens, evaluation of the FNA results showed a predictive value of a positive result of 96.8%. These results compare favorably with those of surgical biopsy. The malignancies present in the lymph nodes included numerous adenocarcinomas from the breast, melanoma and pulmonary small-cell carcinoma. Six cases are briefly presented in which the FNA diagnosis was more problematic. While histologic examination of tissues or organs remains the desirable benchmark of comparison, the appropriate utilization of FNA cytology to guide therapy, particularly in a patient with previously diagnosed malignancy, may obviate the need for an open biopsy. The technique is convenient for patient and physician, useful for outpatients, relatively painless and provides good correlation between cytologic morphology and histopathology.     

Diagnosing Kikuchi disease on fine needle aspiration biopsy: a retrospective study of 44 cases diagnosed by cytology and 8 by histopathology.

OBJECTIVE: To study the accuracy of fine needle aspiration (FNA) diagnosis of Kikuchi lymphadenitis (KL). STUDY DESIGN: Retrospective review of all cases of FNA biopsy of lymph nodes in which KL was diagnosed or suggested. False positive cases were studied. Cases of KL diagnosed by histopathology were examined for the false negative rate of FNA diagnosis. RESULTS: Forty-four cases of KL diagnosed or suggested by FNA were found. Five of eight cases were confirmed on lymph node excision. The false positive rate was 37.5%. One case was nonspecific reactive changes. Two cases were proven to be tuberculous lymphadenitis by culture. Eight cases of KL diagnosed by lymph node excisional biopsy had prior FNA. Four were diagnosed as or suspected to be KL. The false negative rate was 50%. CONCLUSION: The overall accuracy of FNA diagnosis of KL was 56.25%. Detailed study offalse positive cases and knowledge of other conditions suggested that overreliance on certain cytologic features and the morphologic erlap between KL and tuberculous lymphadenitis could have been the reasons for the inaccuracies.     

Fine needle aspiration cytology of neuroblastoma, including peripheral neuroectodermal tumor, with immunocytochemical and ultrastructural confirmation

Eleven fine needle aspiration (FNA) biopsies were performed on seven children with neuroblastoma, including one patient with a congenital neuroblastoma and another with a peripheral neuroblastoma of the thoracopulmonary region. FNA cytology made the primary diagnosis of neuroblastoma in four of the seven cases. The other biopsies documented local recurrences and metastases to liver, lymph nodes, orbit and breast. The cytologic features included varying numbers of small primitive cells with scanty cytoplasm, poorly to well-formed pseudorosettes, cell processes, a fibrillary matrix and multinucleated ganglion cells. Five of the seven patients had electron microscopic (EM) examination of the FNA specimen, which in all cases confirmed the diagnosis. Batteries of immunoperoxidase stains were performed on all 11 aspirates with variable results. Staining for neuron-specific enolase was positive in four of the five neoplasms tested, although strongly positive in only three of the cases. Staining for neurofilament markers was positive in only two of five tumors. Studies for cytokeratin markers (AE1/3), low-molecular-weight cytokeratin (35BH11), hematopoietic markers (T29/33), immunoglobulin light chains and myoglobin were negative. One case was positive for vimentin. This study attests to the value of FNA cytology in suggesting a correct diagnosis of either primary, recurrent or metastatic neuroblastoma in children. Selective use of immunoperoxidase stains and EM on the aspirates may be of value.     

Chromosomal abnormalities and DNA image cytometry of haematological neoplasms in fine needle aspirates of lymph nodes

The current diagnostics of haematological neoplasms along with morphological analysis, immunophenotyping and molecular analysis inevitably includes cytogenetic analysis. In this work the possibility of cytomorphological subclassification of haematological neoplasms from lymph node fine needle aspirates was examined without depending upon the referential histological diagnosis and cytogenetic analysis. In addition, the feasibility of cytogenetic analysis of the material obtained by lymph node fine needle aspiration (FNA) was examined. By analysing the findings of cytogenetic analysis and DNA image cytometry, it was decided to examine the possibility of comparing the findings and supplementing diagnostic possibilities of these methods. In 15 cases cytological diagnoses and cytogenetic analysis of haematological neoplasms were performed on the material obtained by lymph node FNA. In 12 of 15 cases histological diagnosis was made separately. A good cytohistological correlation was available in 9 of 12 cases (75%). Cytomorphological diagnoses in 10 of 15 cases (76%) were confirmed by the finding of a specific chromosomal translocation. In two cases cytological diagnosis did not correlate with the histological diagnosis and was confirmed only with specific chromosomal translocations. The lymphocytes obtained by lymph node FNA were adequate material for cytogenetic analysis - in 15 of 18 (83%) cases mitoses in cell cultures were obtained. In 13 of 15 (87%) cases clonal chromosomal abnormalities were detected, whereas in 2 of 15 (13%) cases a normal karyotype was found. DNA image cytometry was performed on nine samples, whereas in six samples the material was not sufficient. Although a small number of samples was analysed in the cases with identical cytomorphological diagnoses, the analysed histograms regarding the DNA index values showed heterogeneity. In conclusion, a cell culture sampled by FNA of lymph nodes is an adequate method for the chromosomal analysis. The specific cytogenetic abnormality associated with cytological diagnosis provides an opportunity to make a definitive diagnosis and provides a powerful approach when reference diagnosis on biopsy material cannot be obtained.     

Visceral fat accumulation induced by a high-fat diet causes the atrophy of mesenteric lymph nodes in obese mice

Objective: A high intake of fat in the diet plays a crucial role in promoting obesity and obesity‐related pathologies, and especially visceral obesity is closely associated with obesity‐related complications. Because adipose tissue is anatomically associated with lymph nodes, the secondary lymphoid organ, we hypothesized that fat tissue‐derived factors may influence the cellularity of lymphoid tissue embedded in fat. Methods and Procedures: Mesenteric and inguinal lymph nodes were isolated from obese mice fed a high‐fat diet and control mice fed a regular diet. T‐cell population, activation state, and the extent of apoptosis were determined by flow cytometric analysis or terminal deoxynucleotidyl transferase biotin‐dUTP nick end labeling (TUNEL) assay. Results: The weight of mesenteric lymph nodes and the total number of lymphoid cells in the obese mice significantly decreased compared with those in the control mice; however, no change was observed in the weight of inguinal lymph nodes. The numbers of CD4⁺ and CD8⁺ T cells in the mesenteric lymph nodes of obese mice significantly decreased compared with those of the control. Enhanced T‐cell activation and apoptosis were observed in the mesenteric lymph node cells of the obese mice. The treatment of lymph node cells with free fatty acids, oxidative stress, and chylomicrons, which are obesity‐related factors, resulted in lymph node T‐cell activation and apoptosis. Discussion: These results suggest that visceral fat accumulation with a high‐fat diet can cause the atrophy of mesenteric lymph nodes by enhancing activation‐induced lymphoid cell apoptosis. Dietary fat‐induced visceral obesity may be crucial for obesity‐related immune dysfunction.     

Cystic Lymph Nodes in the Lateral Neck As Indicators of Metastatic Papillary Thyroid Cancer

ObjectiveTo determine whether radiographic findings portend to metastatic disease in patients with papillary thyroid carcinoma (PTC) and whether cystic lymph node metastasis can be recognized by preoperative, ultrasound-guided fine-needle aspiration (FNA).MethodsWe performed a retrospective review of patients with cystic lymph nodes in the lateral neck identified on preoperative ultrasonography between March 1996 and December 2009. Factors examined included demographic information; stage; cytologic and final pathologic findings; and imaging characteristics including location, size, and presence of vascularity and calcifications. Time of cystic node identification in relationship to initial diagnosis was also recorded.ResultsThirty patients had cystic lymph nodes in the lateral neck on cervical ultrasonography during the study period. Among this group, 28 (93%) had PTC, 1 (3%) had papillary serous carcinoma of the ovary, and 1 (3%) had poorly differentiated thyroid cancer. Median age at initial cancer diagnosis was 41 years (range, 16-64 years). Twenty-one patients (70%) were women, and median lymph node size was 1.8 cm (range, 0.6-4.8 cm). Twenty-three patients (77%) had a solitary cystic lymph node, and the remainder had more than 1 cystic lymph node. Cystic lymph nodes were identified at initial presentation in 11 patients (37%), while cystic lymph nodes were discovered in 19 patients (63%) after the initial operation. FNA was performed on the cystic lymph nodes of 23 patients (77%). Cytologic findings were positive for metastatic disease in 18 of 23 patients (78%). Among the 5 of 23 patients with negative cytologic findings, thyroglobulin aspirate was obtained in 1 patient, confirming metastatic PTC. Final pathologic review after surgical resection of cystic lymph nodes with negative cytologic findings from FNA was consistent with metastatic disease in 4 of 5 patients (80%).ConclusionsIn patients with PTC, the presence of a cystic lymph node by ultrasonographic examination is highly suggestive of locally metastatic disease. Confirmation of metastatic PTC may sometimes be achieved with thyroglobulin aspirate from cystic lymph nodes when cytologic findings are negative. Clinicians should strongly consider surgical lymph node resection of cystic lymph nodes regardless of the preoperative cytologic findings by FNA. (Endocr Pract. 2011;17:240-244)     

Lipogranulomatous lymphadenopathy as a potential source of error in fine needle aspiration cytology. A case report

BACKGROUND: Lipogranulomatosis refers to the presence, in lymph nodes and spleen, of lipid material arising from endogenous sources, such as tumors, hematomas, cholesterol deposits, fat embolism and fat necrosis. The histologic image is similar to that seen in lymph nodes after lymphography, with vacuolized histiocytes; round, empty spaces; and numerous multinucleated giant cells (MGC). CASE: A 27-year-old woman was referred to our department for fine needle aspiration of bilateral inguinal lymph nodes. One year before, a giant cell tumor of the sacrum was surgically excised at another medical center. The aspirated material showed a normal lymphoid cell background in addition to several MGC and ill-defined cellular groups of mononuclear, histiocytelike cells admixed with mature lymphocytes. After the cytologic report was issued both nodes were surgically excised. The most remarkable histologic finding was the presence of sinus histiocytosis and multifocal subcapsular and sinusoidal lipogranulomas with numerous MGC. CONCLUSION: Lipogranulomatous lymphadenopathy is a rare pathologic condition and may be responsible for smears with numerous MGC. This entity should be considered when evaluating lymph node aspirates from patients with neoplasia, particularly that with a giant cell component.     

Incomplete differentiation of antigen-specific CD8 T cells in tumor-draining lymph nodes

CD8 T cells lacking effector activity have been recovered from lymphoid organs of mice and patients with progressing tumors. We explored the basis for lack of effector activity in tumor-bearing mice by evaluating Ag presentation and CD8 T cell function in lymphoid organs over the course of tumor outgrowth. Early after tumor injection, cross-presentation by bone marrow-derived APC was necessary for T cell activation, inducing proliferation and differentiation into IFN-gamma-producing, cytolytic effectors. At later stages of outgrowth, tumor metastasized to draining lymph nodes. Both cross- and direct presentation occurred, but T cell differentiation induced by either modality was incomplete (proliferation without cytokine production). T cells within tumor-infiltrated nodes differentiated appropriately if Ag was presented by activated, exogenous dendritic cells. Thus, activated T cells lacking effector function develop through incomplete differentiation in the lymph nodes of late-stage tumor-bearing mice, rather than through suppression of previously differentiated cells.     

Antigen-bearing Langerhans cells in skin,dermal lymphatics and in lymph nodes

Ferritin-challenged skin sites and draining lymph nodes were studied in normal guinea pigs and in guinea pigs which had been passively sensitized to ferritin or peroxidase by lymphoid cell transfer to ascertain whether Langerhans cells can bind antigen in skin and carry it to lymph nodes. After intradermal challenge with amounts of ferritin as small at 5 μg, ferritin-containing Langerhans cells were seen by electron microscopy in the marginal sinus and cortex of draining lymph nodes in ferritinscnsitized animals and, to an apparently lesser degree, in control animals. Lymph nodes from unchallenged normal guinea pigs contained rare Langerhans cells, none of which had ferritin. The findings indicate that Langerhans cells may pick up antigen in skin and from there circulate to draining lymph nodes, thus carrying out a function analogous to macrophages. In this way they may exhibit antigen to lymphocytes both in skin and in lymph nodes.