Epithelial cytologic atypia in a fine needle aspirate of an invasive thymoma. A case report.

Fine needle aspiration of a superior-anterior mediastinal mass in a 35-year-old man revealed sheets and clusters of epithelial cells intermingled with a few lymphocytes, characteristic of a thymoma. The presence of atypical cytologic features, such as nuclear pleomorphism, large and vesicular nuclei, prominent nucleoli and frequent mitotic figures, in the epithelial cells caused diagnostic confusion with a thymic carcinoma. However, the subsequent clinical and histologic findings were consistent with an invasive epithelial thymoma. The cytologic features in the present case showed that thymoma with intermediate cytology between that of an ordinary thymoma and thymic carcinoma may be encountered in fine needle aspirates of mediastinal tumors. The cytologic differentiation from a carcinoma may be difficult when the degree of epithelial atypia is high. Histologic confirmation is necessary for a definitive diagnosis.     

Cytopathology of thymoma

From 1967 to 1981, 37 cases were diagnosed as thymoma by transthoracic fine needle aspiration biopsy. All were verified histologically, with no false-positive results. The various cytomorphologic patterns of thymoma are presented. All aspirates from the thymomas were reviewed and found to be composed of epithelial elements, with an admixture of lymphocytes in various proportions. There were 13 cases of lymphocytic predominance, 11 of epithelial-cell predominance, 4 of spindle-cell predominance, and 9 of mixed cell types. In the cytologic preparations the epithelial elements from different tumors exhibited different cytologic appearances and were tentatively subclassified into five types: small, intermediate, large, large pleomorphic and spindle shaped. The cytologic features of thymoma observed in aspiration biopsies are sufficiently distinctive from those of other anterior mediastinal tumors to be diagnostic. It appears feasible to investigate an anterior mediastinal mass with percutaneous fine needle aspiration for the purpose of establishing the diagnosis of thymoma prior to median sternotomy or thoracotomy.     

Diagnosis of cervical thymoma by fine needle aspiration biopsy with flow cytometry. A case report

BACKGROUND: Cervical thymoma is a rare entity. To our knowledge, this is the 20th reported case of cervical thymoma and the fourth case of fine needle aspiration biopsy (FNAB) of this entity. To our knowledge, this is the only case in which cervical thymoma was a diagnostic consideration at the time of the FNAB diagnosis. The diagnosis was rendered because, unlike in previous cases, flow cytometric immunophenotyping was performed. CASE: A 46-year-old, white female presented with what was clinically thought to be a left thyroid nodule. The patient underwent FNAB at an outside institution, and the diagnosis of "possible mixed lymphoma" was made by morphology alone. The patient was referred to our institution for repeat FNAB. Based upon the cytologic findings (cells with lymphoid morphology), flow cytometry was performed, and a diagnosis of cervical thymoma (versus ectopic thymic tissue) was based upon flow cytometry findings combined with morphology. CONCLUSION: When FNAB of a cervical mass, particularly one clinically thought to be a thyroid nodule, shows lymphoid cells without thyroid follicular cells, immunophenotyping may be extremely helpful in arriving at the correct diagnosis.     

Mediastinal masses diagnosed as thymus hyperplasia by fine needle aspiration cytology

OBJECTIVE: Thymic hyperplasia in the anterior mediastinum can occur in healthy children as idiopathic thymic hyperplasia or as a rebound effect after administration of chemotherapy in patients with malignancies. Thymic hyperplasia after chemotherapy is a well-documented phenomenon, particularly in children and less frequently in adults. Both forms of thymic hyperplasia are a diagnostic challenge, and most patients undergo surgical exploration. Fine needle aspiration cytology (FNAC) has supposed to be inadequate to diagnose benign thymic hyperplasia and to separate it from malignant disease. STUDY DESIGN: We report the cytologic findings on eight patients presenting with a mass in the anterior mediastinum that was diagnosed as thymic hyperplasia on FNAC. In five patients the masses developed after chemotherapy. The remaining three patients were healthy children. Three patients underwent ultrasound-guided aspiration; in five cases the procedure was performed under computerized guidance. RESULTS: In all eight patients the cytologic smears showed a mixed population of lymphoid cells. Cytologic diagnosis of thymic hyperplasia was confirmed by immunophenotyping in three patients and by follow-up studies in all of them (median, 68 months; range, 8-113). CONCLUSION: In contrast to previous reports, this study demonstrated the utility of FNAC as a front-line investigative procedure in diagnosing thymic hyperplasia.     

Ectopic hamartomatous thymoma. Report of a case with fine needle aspiration biopsy findings

BACKGROUND: Ectopic hamartomatous thymoma is a rare, benign tumor occurring exclusively in the supraclavicular and suprasternal regions. To the best of our knowledge, there are no English-language reports on its cytologic findings. CASE: A fine needle aspiration specimen from a mass in the suprasternal region in a 63-year-old male revealed epithelial cell nests, spindle cells, a cluster of mature adipocytes and a small number of lymphocytes. CONCLUSION: Although ectopic hamartomatous thymoma is very rare, fine needle aspiration cytology may contribute to the correct diagnosis in conjunction with the characteristic clinical findings.     

Fine needle aspiration cytology of Langerhans cell histiocytosis of the thyroid. A case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) of the thyroid is a rare condition, and fine needle aspiration cytology (FNAC) of this entity has rarely been described. CASE: FNAC was done on a 3-cm-diameter thyroid swelling in the left lower lobe of the thyroid gland. Smears showed a large number of lymphocytes, eosinophils, thyroid follicular cells and discrete, large cells with prominent nuclear grooves. Mitotic activity was frequent. A cytologic diagnosis of LCH was offered. Subtotal thyroidectomy was performed, and the cytologic diagnosis was confirmed by histology. CONCLUSION: LCH of the thyroid has certain salient diagnostic features. The presence of histiocytes with prominent nuclear grooves, reactive lymphoid cells and eosinophils along with benign thyroid follicular cells should raise the suspicion of this rare entity on FNAC smears of the thyroid.     

Fine needle aspiration cytology of follicular dendritic cell sarcoma. A case report

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is a rare, recently described neoplasm that shows differentiation similar to that of follicular dendritic cells. It must be differentiated from metastatic neoplasms and other rare, nonlymphoid nodal lesions. CASE REPORT: A 76-year-old man underwent fine needle aspiration of a recurrent laterocervical mass. Sixteen months earlier, the original tumor was excised and proved to be an FDC sarcoma. Smears exhibited a dual cell population composed of large cells with abundant cytoplasm and a lymphoid component that consisted mainly of lymphocytes and plasma cells. Large cells were atypical and distributed in ill-defined groups and as single cells. Nuclei were round to oval and pleomorphic, with irregular contours and nucleoli. Binucleation and multinucleation were occasionally seen. After the cytologic diagnosis, the tumor was excised and showed typical histologic and immunophenotypic features of FDC sarcoma. CONCLUSION: The morphologic features of FDC sarcoma seem characteristic enough to permit its preoperative recognition. Its cytologic definition increases our knowledge of rare, nonlymphoid, primary nodal tumors, allowing better differentiation from metastatic neoplasms.     

Absence of the Epstein-Barr virus genome in the normal thymus, thymic epithelial tumors, thymic lymphoid hyperplasia in a European population

It has previously been shown that the Epstein-Barr virus (EBV) genome may be detected in some thymic tumors. We have investigated specimens of normal thymus, thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial tumors obtained from european patients for the presence of EBV genome by in situ hybridization and DNA-blotting methods. Cell lines established from seven of the thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of the tumors examined, which included various types of thymoma and thymic carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from Asian patients were included in this study. We suggest that EBV is linked to a specific epithelial tumor type, namely the lymphoepithelial-like carcinoma, regardless of its site, and not to thymic tumors in general.     

Galectin-1 is expressed by thymic epithelial cells in myasthenia gravis

Galectin-1, a member of a family of carbohydrate binding proteins, is synthesized by thymic epithelial cells in normal juvenile thymus, and mediates adhesion of immature T cells to thymic epithelium. Because cell adhesion molecules are proposed to play a role in the thymic hyperplasia and neoplasia seen in the autoimmune disease myasthenia gravis, we examined the expression of galectin-1 in myasthenic thymi. We detected abundant galectin-1 expression in thymic epithelial cells in 27 hyperplastic and neoplastic thymi from patients with myasthenia gravis. Primary cultures of neoplastic epithelial cells from a thymoma continued to express galectin-1, and bound immature T cells; T cell binding was inhibited by the addition of the -galactosides lactose and thiodigalactoside, suggesting that galectin-1 on the thymoma cells and a saccharide ligand on the T cells participated in cell-cell adhesion. Expression of galectin-1 by thymic epithelial cells may play a role in the thymic pathology seen in myasthenia gravis.     

Intraabdominal follicular dendritic cell sarcoma: report of a case with fine needle aspiration findings.

BACKGROUND: Follicular dendritic cell sarcoma is a rare tumor derived from dendritic cells of lymphoid follicles. Although it shows characteristic cytologic, histologic and immunohistochemical features, it may be misdiagnosed because of the lack of experience with this entity. There are few reports in the cytologic literature describing this entity. CASE: A left hypochondrial mass was found in an 80-year-old man who had a past history of colonic carcinoma. A computed tomography-guided fine needle aspiration biopsy was performed, and the findings were initially thought to be compatible with metastatic carcinoma. The mass was excised, and a diagnosis of follicular dendritic cell sarcoma was made. CONCLUSION: Follicular dendritic cell sarcoma is characterized by loosely cohesive or syncytial groups of dendritic cells that show oval, vesicular nuclei and ill-defined cytoplasm intimately admixed with small, mature lymphocytes. The diagnosis can be confirmed by positive immunostaining for CD21 and CD35 antigens and negative staining for cytokeratin. Unusual features in our case were the presence of prominent plasma cells and intracytoplasmic, periodic acid-Schiff stain, diastase-positive deposits, with the last not described before.     

Establishment of functional epithelial cell lines from a rat thymoma and rat thymus

Summary Seven clonal epithelial cell lines from a thymoma of an (ACI/NMs×BUF/Mna)F1 rat and seven clonal epithelial cell lines from an ACI/NMs rat thymus were established in a medium containing 1 μM dexamethasome (DM) and were characterized cytologically. Long-term treatment of DM stabilized the epithelial nature of these epithelial cells irreversibly. The established cell lines showed a polygonal shape, were positively stained with antikeratin antiserum and had tonofilaments and desmosomes. Species of their keratin paptides were the same as those of normal thymic epithelial cells in primary cultures. The cell lines were positively stained with Th-4 monoclonal antibody which preferentially stains the medullary epithelial cells of the thymus, but not with Th-3 which preferentially stains the subcapsular and cortical epithelial cells of the thymus. The cells from the rat thymoma were much large than those from the normal thymus, as reflected in their primary cultures. No transformed phenotypes, such as high growth rate, high saturation density anchorage independency, low serum dependency and so on, were found on the cell lines from the thymoma as in the cell lines from the normal thymus by in vitro assays. DNA synthesis of the thymic lymphocytes was stimulated by culturing with a line of rat thymoma with no lectins. Thymic lymphocytes strongly bound on the cell lines from the thymoma and changed the shape of the cells. These cell lines may be useful to investigate the mechanism of thymomegenesis and the interactions between epithelial cells and thymocytes in the rat thymoma.     

Absence of the Epstein-Barr virus genome in the normal thymus,thymic epithelial tumors,thymic lymphoid hyperplasia in a European population

It has previously been shown that the EpsteinBarr virus (EBV) genome may be detected in some thymic tumors. We have investigated specimens of normal thymus, thymitis with lymphoid hyperplasia and a large spectrum of thymic epithelial tumors obtained from european patients for the presence of EBV genome by in situ hybridization and DNA-blotting methods. Cell lines established from seven of the thymic tumors were also tested for EBV. No EBV genome was demonstrated in any of the tumors examined, which included various types of thymoma and thymic carcinomas, nor in the non-neoplastic thymic specimens. However, unlike previous reports, no examples of lymphoepithelial-like thymic carcinoma, nor specimen from Asian patients were included in this study. We suggest that EBV is linked to a specific epithelial tumor type, namely the lymphoepithelial-like carcinoma, regardless of its site, and not to thymic tumors in general. Supported by the SFB 172, C8, grant to BB and by the Deutsche Forschungsgemeinschaft, grant Ki 370/1-1     

Expression and gene rearrangement of the T-cell receptor in human thymomas

Human thymomas are epithelial neoplasms frequently associated with an exuberant lymphoid component. This mixture of epithelial cells and lymphocytes closely mimicks the organization of normal thymic cortex. However, it is not known whether thymocytes in thymoma express the T-cell receptor (TCR) for the antigen. We have analyzed the molecular configuration of TCR genes and their phenotypic expression in eight thymomas. In all we detected polyclonal rearrangements of TCR genes and cytoplasmic expression of TCR molecules in most thymocytes, thus indicating that rearranged TCR genes in thymomas are functioning genes. In addition, these findings suggest that the epithelial component of thymomas, even if neoplastic, is still capable of directing thymocyte differentiation.     

Diagnosis of thymoma by needle biopsy.

One cutting needle biopsy specimen and six fine needle aspiration biopsy specimens of thymomas were studied in order to define diagnostic criteria for this entity in biopsy material. Two of the cases demonstrated a mixed pattern of epithelial cells and lymphocytes while epithelial cells predominated in four cases and lymphocytes in one. Tumors composed of a conspicuous admixture of benign-appearing epithelial cells and mature lymphocytes were easily diagnosed. Neoplasms composed primarily of one cell type also displayed distinctive cytologic features that correlated with the histopathologic appearance of the resected tumors and permitted a diagnosis. Immunocytochemical demonstration of keratin and T6 proved useful in confirming the biphasic pattern of epithelial cells and cortical thymocytes that is characteristic of thymoma.     

Incidental Radiologic Finding of an Anterior Superior Mediastinal Mass Masquerading as Metastatic Thyroid Cancer in Patients with Treated Thyroid Cancer

ObjectiveTo demonstrate that an anterior superior mediastinal mass on radiologic imaging may represent an incidental finding and not metastases in patients with a history of treated well-differentiated thyroid cancer.MethodsWe report the clinical presentation and outcomes of 4 patients with a history of thyroid cancer who were incidentally found to have anterior superior mediastinal masses on imaging. We also review the relevant literature.ResultsFour young adults with a history of stage I papillary thyroid cancer treated with total thyroidectomy and radioiodine were incidentally found to have thymic enlargement on imaging studies within a 3-year posttreatment window. In each case, this enlargement was believed to be secondary to thymic hyperplasia and not metastatic disease, and each patient has exhibited a benign clinical course. Review of the literature revealed few reports of an association between thymic hyperplasia and thyroid cancer.ConclusionsThymic hyperplasia may be discovered on posttreatment imaging studies in patients with a history of well-differentiated thyroid cancer, particularly in young adults who have received radioiodine therapy. Recognition of the possible coexistence of this incidental finding in patients with thyroid cancer may help to avoid unnecessary invasive procedures and treatments. (Endocr Pract. 2011;17:65-69)     

Quantitative image analysis of immunohistochemical stains using a CMYK color model

Background

The current study correlates cytologic morphology with histologic type and describes immunophenotypes with a focus on epithelial, neuroendocrine, and lymphoid characteristics in an institutional series of surgically excised thymomas.

Methods

Fine needle aspirates (FNAs) and surgical specimens were retrospectively analyzed, and immunohistochemical stains were performed for EMA, cytokeratin 7, cytokeratin 20, CD57 CD5, bcl-2, calretinin, vimentin, CD3, CD20, CD1a, CD99 and Ki67. Tumors were classified by WHO criteria.

Results

There were eleven male and six female patients with an age range of 41 to 84 years (mean, 61 years) and a male to female ratio of 1.8:1. Four thymomas (4/17, 23.5%) were associated with neuromuscular disease: myasthenia gravis (n = 3) and limbic encephalitis (n = 1). FNA, under CT guidance, was performed in 7 cases. The positive predictive value for thymoma by FNA cytology was 100% and the sensitivity was 71%. Thymomas associated with neuromuscular disorders were WHO types B2 (n = 1) and B3 (n = 3), and showed a strong expression of CD57 in the majority of neoplastic epithelial cells accompanied by large numbers of CD20+ intratumoral B lymphocytes. Two of seventeen (11.7%) thymomas (all sporadic B3 type) contained numerous neoplastic epithelial cells positive for CD5 and bcl-2.

Conclusion

Our results suggest that thymomas associated with autoimmune disorders contain a significant population of CD20+ intratumoral B lymphocytes. Strong CD57 positivity in thymomas may suggest a concomitant neuromuscular disorder, notably myasthenia gravis. CD5 expression is of limited value in the differential diagnosis of primary thymic epithelial neoplasms since both thymic carcinomas and thymomas may express CD5.     

Thymus-derived lymphocyte differentiation and lymphocytic leukemias. I. Evidence for the existence of functionally different subpopulations of thymus-derived cells in leukemic AKR mice

The effects of transplanting thymic (LTC), splenic (LSC), and lymph node (LLNC) lymphocytes derived from overtly leukemic AKR mice into preleukemic syngeneic animals were studied. Each of these thymus-derived (T cell) populations produced a different and distinct pathology in recipient mice. Animals receiving LTC exhibited thymoma and enlargement of peripheral lymphoid tissues. Gross organomegaly was also noted in mice given LSC, but thymic atrophy was uniformly observed. The thymus appeared normal in mice receiving LLNC, but marked enlargement of peripheral lymphoid tissues again were observed. The differences noted in disease pathologies correlated with the “homing” patterns of the subpopulations investigated. These findings suggest that subpopulations of T cells exist in mice with a thymus-derived neoplastic disorder.     

Microenvironment of thymic myoid cells in myasthenia gravis

The microenvironment of myoid cells (MyCs) was studied in myasthenia gravis (MG) thymitis with lymphoid follicular hyperplasia (LFH) (nine cases) and with diffuse B cell infiltration (one case), and compared with findings in the thymuses of non-myasthenic control subjects (ten cases). Double immunostaining was used to demonstrate MyCs labelled by anti-desmin together with other thymic components such as keratin-positive epithelial cells, Ki-M 1-positive interdigitating reticulum cells (IDCs), Ki-M 4-positive follicular dendritic reticulum cells, Ki-M 6-positive macrophages, CD22-positive B-cells, CD1-positive cells, CD3-positive T-cells or HLA-DR-positive cells. Round or elongated MyCs were confined to the thymic medulla and were surrounded by CD3-positive T-cells and CD22-positive B-cells. In MG thymitis MyCs were localized in the vicinity of, but not inside germinal centres (GCs). MyCs were always HLA-DR-negative, but were invariably embedded in a cellular micromilieu with strong HLA-DR expression. A remarkable feature of MG thymitis was that the great majority of MyCs were in intimate contact with intramedullary IDCs. Morphometric studies confirmed that such contacts were significantly less frequent in thymuses from non-myasthenic subjects. This indicates that an IDC-dependent antigen-presenting process for T-cells may actively involve MyCs in MG thymitis.     

Endodermal sinus tumor of the mediastinum. Cytologic diagnosis on a pleural effusion

A primary mediastinal endodermal sinus tumor in a young man was diagnosed by cytologic examination of a pleural effusion. Subsequent evaluation revealed a greatly elevated serum alphafetoprotein (AFP); computed tomographic scan of the chest showed a large anterior mediastinal mass. Routine examination of the smears and cell block preparations revealed clusters of tumor cells with a few intracytoplasmic hyaline droplets. Immunohistochemical stains for AFP, alpha-1-antitrypsin and cytokeratin were positive in the tumor cells while stains for carcinoembryonic antigen and the beta subunit of human chorionic gonadotropin were negative. This supported the diagnosis of endodermal sinus tumor, a rare primary tumor within the mediastinum.     

Cystic adult ovarian granulosa cell tumor as a potential source of false negative diagnosis in ovarian cytology. A case report

BACKGROUND: Adult granulosa cell tumors (AGCT), unilocular or multilocular, with thin-walled cysts, are extremely rare. They can be erroneously diagnosed as follicular cysts by sonography and fine needle aspiration and therefore may be a source of false negative results. CASE: Laparoscopy was performed on a 29-year-old woman in whom a cystic ovarian mass, probably benign, was diagnosed by transvaginal sonography. The smears obtained from the cyst revealed a moderate amount of regular, small cells with scant cytoplasm and round to oval nuclei with finely granular chromatin without longitudinal grooves. These granulosa cells were arranged singly and in small groups. Very scarce cellular aggregates, microfollicular or rosettelike, some containing amorphous material and resembling Call-Exner bodies, were identified. Histologic study of the cystic wall confirmed the diagnosis of multilocular cystic AGCT with a microfollicular pattern. CONCLUSION: The finding of a moderate to abundant amount of regular granulosa cells, with or without nuclear longitudinal grooves, during cytologic examination of ovarian cysts considered benign by ultrasonography requires a careful search for microfollicular differentiation and Call-Exner bodies due to the rare but possible occurrence of cystic AGCT.