[Morphological features of pulmonary and thymic carcinoid tumor].

Morphological features of atypical and typical subtypes of pulmonary and thymic carcinoid tumors have been studied by pathohistological, immunohistochemical and electron-microscopic methods. There are the main principles of differential diagnostics in the article.

[Pathological features and ultrastructure of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice].

The objective of study was to investigate the origin and to classify the subtype of N-methyl-N-nitrosourea (MNU)-induced thymic lymphomas in mice. Histopathologic, immunohistochemical and ultrastructural studies were performed to analyze the pathological features of the neoplasms. The results showed that the thymus in all cases became totally replaced by sheets of cells of the lymphoid series. All the tumors coexpressed CD3 and TdT. Transmission electron microscopic study showed the plasma membranes of malignant lymphoma cells were smooth. The nuclear profiles were usually regular, with varying percentage of convoluted nuclei. Few cell organoids were observed in cytoplasm. In conclusion, all the MNU-induced tumor classified by histopathologic, immunohistochemical and ultrastructural studies as precursor lymphoblastic lymphoma that were unquestionably related to the thymus origin and T-cell lineage.

Mediastinal thymolipoma: a rare occurrence with striated myoid cells.

We describe a 49-year-old man who presented to hospital with unstable angina and who underwent emergency coronary artery bypass grafting. During the surgical procedure, an incidental anterior mediastinal mass was discovered. Histological examination of this mediastinal mass revealed a thymolipoma containing numerous polygonal, striated myoid cells that were immunoreactive for desmin, muscle-specific actin and myoglobin. Electron microscopy demonstrated numerous Z band structures confirming myoid differentiation. Even though the appearance of myoid cells in thymolipoma may be alarming, this tumor should be recognized as a benign entity. Thymolipomas containing striated myoid cells should be differentiated from more ominous thymic neoplasms, including teratomas and thymic liposarcomas. To our knowledge, this is only the third reported case of thymolipoma containing striated myoid cells.

[Clinicopathologic study of metaplastic thymoma].

OBJECTIVE: To study the clinicopathologic characteristics of metaplastic thymoma. METHODS: Resection specimens of 3 cases of metaplastic thymoma were studied by light microscopy, immunohistochemistry and electron microscopy. RESULTS: All the 3 patients were females and aged 33, 58 and 45 years respectively. Histologically, a biphasic growth pattern, consisting of intimate admixture of epithelial cells and spindle cells, was noted. The epithelial cells showed mild cytologic atypia, sometimes nuclear grooves and pseudonuclear cytoplasmic inclusions. These cells were arranged in nests and anastomosing cords. Mitotic figures were rarely seen. On the other hand, the spindle cells were bland-looking, mitotically inactive and arranged in fascicles. Immunohistochemical study showed that the epithelial cells strongly expressed cytokeratin (AE1/AE3) but not vimentin or CD5. The proliferation index, as demonstrated by Ki-67 immunostaining, was about 3% to 5%. In contrast, the spindle cells were diffusely positive for vimentin and epithelial membrane antigen. Staining for CD5 and CD20 was negative. The background lymphocytes were positive for CD3, but not for TdT and CD99. Ultrastructurally, well-formed desmosomes or hemidesmosomes were identified in the epithelial element. They were not detected within the spindle cells. CONCLUSION: Metaplastic thymoma is a rarely encountered indolent or low-grade thymic tumor and may represent a distinct clinicopathologic entity.

Ectopic hamartomatous thymoma: a case report showing CD99+ lymphocytes and a low proliferation index.

Ectopic hamartomatous thymoma is a rare benign tumor that consists of spindle, epithelial, and adipose cell elements. We present a case of this lesion arising in the supraclavicular region of a 59-year-old man, including the characteristic immunohistochemical and ultrastructural findings. DNA flow cytometry revealed diploidy with a low proliferation index (6.73%). The tumor contained CD99+ lymphocytes; CD99 (MIC2) can serve as a useful marker of immature T cells. These findings suggest that ectopic hamartomatous thymoma may develop from the third branchial pouch or thymic anlage.

Sex steroid hormone receptors in human thymoma.

In this study we examined the immunohistochemical localization of sex steroid receptors for estrogen alpha (ER alpha) and ER beta, progesterone-A (PR-A) and PR-B, and androgen (AR) in human thymoma (n = 132) and correlated these findings with various clinicopathological parameters. We used RT-PCR and real-time PCR to further study the expression of these receptors in 20 thymoma cases. Immunoreactivity for all sex steroid receptors was detected in the nuclei of thymoma epithelial cells. The percentage of immunopositive cases and the H-score values for each receptor (mean +/- SD) were: ER alpha, 66% and 85.8 +/- 80.2; ER beta, 7% and 7.2 +/- 8.7; PR-A, 4% and 2.7 +/- 4.9; PR-B, 49% and 55.8 +/- 68.3; and AR, 15% and 14.1 +/- 11.7, respectively. The results of real-time PCR were consistent with those of immunohistochemistry, especially results for ER alpha, PR-B, and AR. A significant positive correlation was detected between immunoreactivity for ER alpha and PR-B. ER alpha immunoreactivity was inversely correlated with tumor size, clinical stage, WHO classification, and Ki-67 labeling index. In addition, the status of ER alpha immunoreactivity was significantly associated with a better clinical outcome in thymoma patients. Results from our study suggest that estrogens may inhibit thymoma growth via ER alpha, and that ER alpha immunoreactivity may act as a prognostic factor in human thymoma.

Thymic carcinoma with rhabdoid features.

A case of thymic carcinoma with rhabdoid differentiation is presented. A 67-year-old man who presented with chest pain and hemoptysis was referred to The University of Texas M. D. Anderson Cancer Center (Houston, TX). Radiologic studies revealed a large anterior mediastinal mass. After the initial biopsy and preoperative chemotherapy, a radical thymectomy revealed a stage III thymic carcinoma with a rhabdoid component. The rhabdoid component was characterized by large cells with an eccentric nucleus, prominent nucleolus, and typical paranuclear cytoplasmic inclusions. Immunohistochemical and electron microscopic studies confirmed the presence of rhabdoid cells with the paranuclear cytoplasmic inclusions staining for both pancytokeratin and vimentin. The patient was given postoperative chemotherapy and radiation. He has since developed metastases to the pelvis and is alive with disease at 20 months of follow-up. To our knowledge, this is the first reported case of thymic carcinoma with rhabdoid features.

Age changes of neuromuscular junctions in the extensor digitorum longus muscle of spontaneous thymoma BUF/Mna rats. A scanning and transmission electron microscopic study.

BUF/Mna rats spontaneously develop thymomas and cause muscle weakness of hind legs at an advanced age. This rat strain has been recognized as a suitable animal model for human myasthenia gravis or related myopathies. To characterize the structural changes of neuromuscular junctions (NMJs) in BUF/Mna rats, subneural apparatuses (SNAs) of extensor digitorum longus muscles of young-adult (4-month-old) and aged (22- to 25-month-old) male rats were examined using scanning and transmission electron microscopy. The SNAs of NMJs in young rats consist of complex labyrinthine gutters with numerous slit-like junctional folds. SNAs in aged BUF/Mna rats, however, are characterized by: (1) a group of cup-like depressions with very wide slit-like junctional folds in relatively large muscle fibers (the major type), (2) the presence of slit-like folds on the flat sarcoplasm outside the cup-like depressions or on the protruded sarcoplasm, and (3) winding gutters or a small number of round depressions with poorly developed synaptic folds in small and medium-sized muscle fibers (the minor type). Since similar structural changes have been reported in dystrophic mice or normally aged rats, it is suggested that both the slowly progressing muscle atrophy and age-dependent turnover of muscle fibers may occur in the aged BUF/Mna rats.

Granulocytic sarcoma of the thymus in a nonleukaemic patient.

We report a case of granulocytic sarcoma arising from the thymus in a 17-year-old nonleukaemic patient. The patient presented with an anterior mediastinal tumour and underwent surgical resection. Histological examination showed a diffuse infiltrate of immature round cells in the thymus. Tumour cells were diffusely peroxidase positive, but naphthol AS-D chloroacetate esterase negative. Immunohistochemical staining revealed expression of CD34 and terminal deoxynucleotidyl transferase (TdT), but not of CD13 and CD33. Ultrastructurally, electron-dense or medium-density granules were present in the cytoplasm. Four months after successful autogenic bone marrow transplantation, pleural and pericardial fluid contained tumour cells with azurophilic granules, which expressed CD13 and CD33, but not CD34 and TdT. The patient died of the disease 18 months after clinical manifestation, but still without developing leukaemia. The granulocytic sarcoma in the present case may have originated from myeloid precursors in the thymus and remained within the extramedullary site despite the differentiation into a more committed myeloid lineage at the relapse.

Thymic carcinoma with neuroendocrine differentiation in a calf.

A neuroendocrine carcinoma originating in the thymus was found in a 7-month-old, castrated male, Japanese Black calf. The neoplasm consisted largely of very primitive cells, characterized by the paucity of cytoplasmic organelles, but a few cells were immunoreactive for somatostatin or neurofilaments. The expression of both cytokeratin and neurofilament protein was a feature of neuroendocrine differentiation. This neoplasm considered to be a tumor of a thymic stem cell, with little but indubitable evidence of differentiation into somatostatin-producing cells.

Thymic carcinoma of the thymic hormone secretory type in a cow.

An 8-year-old Holstein cow had tumor nodules and enlarged lymph nodes in the mediastinum, and metastatic tumor masses in the pelvic cavity. The neoplastic cells were characterized by squamous features and intracytoplasmic vacuoles carrying microvilli, some of which contained periodic acid Schiff-positive globular cores, but tubular structures or goblet cells were absent. Many neoplastic cells stained positively for keratin, and occasional cells were positive for thymosin. The presence of secretory granules in the cytoplasm was confirmed by electron microscopy. This neoplasm was considered to be of thymic hormone-secreting epithelial cell origin.

Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma.

To determine the neuroendocrine (NE) features of thymic epithelial tumor, immunohistochemistry and electron microscopy studies were performed on eight NE tumors (thymic carcinoids) and 26 non-NE tumors (nine thymic carcinomas, five atypical thymomas, and 12 thymomas other than lymphocytic thymoma). Immunohistochemical studies were performed with antibodies against general markers for NE cells (synaptophysin, alpha subunit of a guanine nucleotide-binding protein, Go, and small-cell lung carcinoma cluster 1 antigen), and a broad panel of antibodies for hormonal substances. Thymic carcinoid showed synchronous diffuse immunoreactivity for the three NE markers and contained cells that were positive for a variety of hormonal products: human chorionic gonadotropin (hCG) alpha-subunit (eight of eight), hCG beta-subunit (three of eight), adrenocorticotropic hormone (ACTH) (three of eight), calcitonin (two of eight), calcitonin gene-related peptide (two of eight), and serotonin (one of eight). Conversely, although positivity for NE markers was neither synchronous nor diffuse in non-NE tumors, seven of nine thymic carcinomas, three of five atypical thymomas (focal or dispersed distribution), and none of the five thymomas were positive for at least two of these NE markers. A small number of neoplastic cells were positive for hCGalpha-subunit or ACTH in three thymic carcinomas and one atypical thymoma. Ultrastructurally, dense core granules (DCG) were much more frequent in thymic carcinoid, but several DCG-like granules were identified in 12 of 13 non-NE tumors with or without immunoexpression of NE markers. The presence of focal or dispersed NE cells in thymic carcinoma and atypical thymoma may reflect multidirectional differentiation within the tumor, which, like cytological atypia, epithelial CD5 expression, and lack of immature T cell infiltration, may be another feature of this group at thymic tumors.

Thymic carcinoid. Report of a case with diagnosis by fine needle aspiration biopsy.

BACKGROUND: Fine needle aspiration biopsy (FNAB) affords a less expensive, less morbid approach to masses within the complex anatomy of the mediastinum as opposed to surgical biopsy. Given the current state of computed tomography guidance and the available cell block preparations and ancillary studies, definitive diagnosis of mediastinal tumors is possible. CASE: A 19-year-old male presented with weight loss and muscle weakness. Computed tomography revealed an anterior superior mediastinal mass with attachment to the posterior sternum and anterior aorta. FNAB yielded hyperchromatic cells with densely clumped chromatin and prominent nucleoli. These were present as single cells and clusters. Cell block preparations were studied with immunoperoxidase methods and were strongly positive for chromogranin and glucagon, supporting the diagnosis of carcinoid tumor. Surgical excision yielded a 7-cm, unencapsulated, red-brown tumor with medium-sized cells with oval to round nuclei, scant and granular cytoplasm and coarse "salt and pepper" chromatin with prominent nucleoli. The cells were arranged in islands and bands and were associated with prominent capillaries and dense, collagenous septae. Immunoperoxidase and electron microscopy demonstrated numerous intracytoplasmic, nonspecific neurosecretory granules and positivity for somatostatin, synaptophysin, cytokeratin and chromogranin. CONCLUSION: FNAB affords an accurate and timely diagnosis of an anterior mediastinal tumor without the necessity for open biopsy and also offers accurate surgical planning and decreased morbidity.

Thymoma with pseudosarcomatous stroma: report of an unusual histologic variant of thymic epithelial neoplasm that may simulate carcinosarcoma.

Six cases are described of an unusual type of primary thymic epithelial neoplasm characterized by a biphasic epithelial/spindle cell morphology that closely resembled a carcinosarcoma. The patients were two women and four men 28-70 years of age. The tumors presented clinically as asymptomatic anterior mediastinal masses found incidentally on routine chest radiographs. All patients were treated by complete surgical excision. Grossly, the tumors consisted of well-circumscribed, encapsulated masses that measured 6-14 cm in greatest diameter and showed a gray-white, homogeneous, rubbery cut surface. Histologically, the lesions were composed of anastomosing islands and cords of oval to polygonal epithelial cells displaying large nuclei with occasional prominent nucleoli and rare mitotic figures, separated by areas containing a highly cellular spindle cell proliferation without nuclear atypia. Thymic remnants could be identified in the periphery of the lesions in four cases. Immunohistochemical stains showed diffuse strong positivity for keratin and focally for epithelial membrane antigen (EMA) in the epithelial cell component, and strong positivity for vimentin and focally for actin in the spindle cell stromal component. Stains for keratin, EMA, desmin, S-100 protein, and CD34 were negative in the spindle stromal cells in all cases except one, in which EMA positivity was present; CD5 stains were negative in the epithelial cells in all cases examined. Electron microscopic examination in one case showed well-formed desmosomes and tonofilaments in the epithelial elements, as well as features indicative of fibroblastic differentiation in the spindle stromal cells. Because of the unusually florid spindle cell stromal component and the focally atypical features of the epithelial cells, some of these tumors initially were misinterpreted as examples of carcinosarcoma. Clinical follow-up in five cases showed that the patients were alive and without evidence of disease over a period of 5-20 years (mean follow-up 10 years), suggesting a benign or very low grade malignant biologic behavior. The present cases appear to represent an unusual, previously undescribed morphologic variant of thymoma characterized by a prominent pseudosarcomatous stromal component. Because of the distinctive histologic appearance and indolent clinical behavior, these lesions should be distinguished from other more aggressive anterior mediastinal neoplasms displaying a biphasic morphology.

Clear cell neoplasms of the endocrine system and thymus.

Clear cell tumors of the endocrine system and thymus are rare lesions with which surgical pathologists have only infrequent contact. As a result, these neoplasms may be misinterpreted and incorrectly classified. This review considers the histological, immunohistochemical, and ultrastructural features of clear cell pituitary adenomas, parathyroid tumors, pancreatic endocrine neoplasms, adrenocortical proliferations, and thymic malignancies. Emphasis is placed throughout on differential diagnosis with microscopically-similar lesions. Clear cell endocrine tumors and thymic lesions manifest a variety of potential lineages, including examples with epithelial, neural, germ cell, and lymphoid differentiation. Because of the wide differences in behavior and recommended treatment in this group, accuracy in diagnosis is essential.

Immunohistochemical and in situ hybridization detection of growth-hormone-producing cells in human thymoma.

We have studied 25 thymomas by both immunohistochemistry and in situ hybridization for the presence of growth hormone (GH)-producing cells. Our results indicate that 1) GH-immunoreactive cells were present in 13 of 17 thymomas of cortical and predominantly cortical type but not in medullary (spindled) thymomas (n = 3) or low- to high-grade thymic carcinomas (n = 5), 2) GH-positive cells were mainly located at the periphery of the neoplastic lobules, at the periphery of the perivascular spaces and in the areas of medullary differentiation, 3) cells containing GH mRNA appeared at locations similar to those of GH-immunoreactive cells, and 4) GH-immunoreactive material was present only in the epithelial cell component as revealed by immunoelectron microscopy. In conclusion, this paper demonstrates the occurrence of GH-producing cells in noncarcinoid thymic tumors. The relevance of GH in thymoma cell biology requires additional investigations.

Spindle epithelial tumor with thymus-like differentiation: a case report with cytologic, histologic, immunohistologic, and ultrastructural findings.

Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a rare and distinctive low-grade neoplasm of thymic or related branchial pouch differentiation. The tumor usually presents in the thyroid or lateral neck of children and adolescents and could mimic spindle-cell carcinoma, synovial sarcoma, or malignant teratoma. We report the clinical, cytologic, histologic, immunohistochemical, and ultrastructural features of a SETTLE present for 10 years in a 15-year-old boy. The fine-needle aspirate, initially interpreted as synovial sarcoma, contained numerous clusters of bland spindle cells, with a few detached sheets of columnar mucous cells in a homogeneous background of dissociated spindle cells. Mitoses, necrosis, and atypia were not present. The excised tumor was a well-circumscribed, white-tan mass, with occasional microcysts. Microscopically, the mass consisted of a lobulated, highly cellular, spindle-cell neoplasm arranged in intersecting, whorled, and storiform fascicles separated by fibrous bands. Entrapped within the fibrous bands were squamous-lined cysts and benign-appearing glands lined by columnar epithelium with goblet cells or ciliated pseudostratified epithelium. Immunohistochemically, the spindle cells showed diffuse reactivity for cytokeratins, smooth muscle actin, muscle-specific actin, and MIC-2, and they were negative for epithelial membrane antigen, calcitonin, and thyroglobulin. Ultrastructurally, numerous perinuclear tonofilaments, some aligned with mature desmosomes, were identified in the spindle cells. Occasional cells showed thin filaments with fusiform dense bodies occupying the peripheral cytoplasm. These findings distinguish SETTLE from ectopic thymoma, synovial sarcoma, medullary carcinoma, and teratoma, and they support a thymic epithelial origin for SETTLE, possibly with myoepithelial differentiation.

Spindle-cell thymic carcinoid occurring in multiple endocrine neoplasia I: fine-needle aspiration findings in a case.

Thymic carcinoid tumors are important to distinguish from thymomas because of their worse prognosis. These rare tumors occasionally occur in the setting of multiple endocrine neoplasia (MEN). A needle biopsy was performed on a 57-yr-old woman with MEN I and a newly-discovered anterior mediastinal mass. Aspiration smears were cellular and contained polygonal-to-spindled cells with high nucleocytoplasmic ratios and evenly-dispersed pattern. Occasional nuclear molding and rosette-like arrangements were present. A synaptophysin immunostain was positive on cell-block preparation. A diagnosis of thymic carcinoid was made. Subsequent excision of the mass confirmed the diagnosis of thymic carcinoid. Thymic carcinoids are cytologically similar to carcinoid tumors elsewhere. They should be distinguished from epithelial thymoma and substernal medullary carcinoma of the thyroid.

Thymic basaloid carcinoma: a case report and review of the literature.

We report a case of thymic basaloid carcinoma in a 65-yr-old man who presented with symptoms referable to the mass effect of the tumor. The tumor arose in association with a multilocular thymic cyst and microscopically was characterized by islands, nests, and cords of basaloid cells. The tumor cells demonstrated prominent palisading around most of the neoplastic islands and nests. The tumor was excised, and there was no evidence of recurrent or metastatic disease in the 6-mo follow-up period. Including the current case, seven cases of basaloid thymic carcinoma have been reported in the English literature, four of which (57%) were associated with a multiloculated thymic cyst. Follow-up was available on three patients. Although no patient has died of tumor, pulmonary metastases developed in two patients. Although basaloid thymic carcinoma is currently considered a tumor of low-grade histology, more cases need to be studied to determine the long-term prognosis of these tumors.