Solitary fibrous tumor of the anterior mediastinum: a rare extrapleural neoplasm.

Solitary fibrous tumors are uncommon spindle cell neoplasms originally thought to be restricted to the pleura. We describe a 62-year-old woman who presented with stridor and an anterior mediastinal mass. At thoracotomy, a 10.5 x 6.5 x 5.5 cm, circumscribed, firm mediastinal mass demonstrated no direct cardiac or pulmonary involvement. The tumor consisted of spindle cells organized in a patternless pattern with collagenous stroma and hemangiopericytoma-like vessels. Spindle cells were immunoreactive for CD34, CD99, desmin, vimentin and bcl-2 protein and a diagnosis of mediastinal solitary fibrous tumor was confirmed. The differential diagnosis of mediastinal solitary fibrous tumors is extensive and includes spindle cell thymoma, sarcomatoid carcinoma, malignant mesothelioma, inflammatory myofibroblastic tumor, peripheral nerve sheath tumors and various sarcomas. Despite their rarity in the mediastinum, solitary fibrous tumors can be recognized by their classic patternless morphology and immunophenotypic pattern. Their accurate classification is important, as solitary fibrous tumors are intermediate (rarely metastasizing) neoplasms that require complete surgical excision and long-term clinical follow-up for optimum therapy.

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.

Cystic adenomatoid tumor of the mediastinum.

A case of adenomatoid tumor presenting as a mass in the anterior mediastinum is described. The patient was a 56-year-old woman with left side chest wall pain who showed a mediastinal mass on chest x-ray and CT scans. Thorough clinical and radiographic examination did not reveal any evidence of tumor elsewhere. At surgery, the tumor was found adjacent to the anterior pericardial reflection. Grossly, the tumor measured 5.5 x 5.5 x 3 cm and showed a homogeneous cut surface with numerous cystic structures that varied from 0.5 to 1.5 cm in greatest diameter. Histologic examination showed numerous cystic spaces lined by flattened or cuboidal epithelial cells. The walls of the cysts showed a proliferation of small canalicular structures lined by round to polygonal epithelioid cells with vacuolated eosinophilic cytoplasm. Immunohistochemical studies showed strong positivity of the epithelioid cells for AE1/AE3 cytokeratin, CK5/CK6, and calretinin. Stains for CK7, CK20, alpha-fetoprotein, CD31, carcinoembryonic antigen, MOC 31, and chromogranin were negative. Electron microscopic examination showed numerous long microvilli on the cell surface and abundant tonofilaments/desmosomal plaques in the tumor cells, characteristic of mesothelial cells. The patient is alive and well and free of recurrence 1 year following surgery. Adenomatoid tumor is a rare neoplasm that should be added in the differential diagnosis of anterior mediastinal masses. Immunohistochemical and ultrastructural studies may be of aid in identifying the characteristic features of mesothelial cells and to avoid mistaking this lesion for more ominous conditions.

Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review.

Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31-73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2-20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.

Leiomyosarcoma arising from soft tissue tumor of the mediastinum.

The occurrence of a leiomyosarcoma (LMS) in soft tissue of the mediastinum is rare. We report a 60-year-old woman with an LMS in mediastinal soft tissue who died 8 months after surgical removal. Pathological, immunohistochemical, and electron microscopic features of this rare tumor are described.

Cytokeratin-positive malignant tumors with reticulum cell morphology: a subtype of fibroblastic reticulum cell neoplasm?

Cytokeratin-positive interstitial reticulum cells (CIRCs) have been described as a subset of fibroblastic reticulum cells (FBRCs) normally found in lymph nodes, the spleen, and tonsils. Although tumors derived form other reticulum (dendritic) cells, specifically follicular dendritic cells, interdigitating dendritic cells, and cytokeratin-negative FBRCs, have been well documented and are now accepted, this is not the case for tumors of CIRCs. A possible reason for this failure is the difficulty in distinguishing them from other tumors, particularly carcinoma. We report three cases of cytokeratin-positive malignant tumors with a reticulum cell morphology: two located in the mediastinum and one in the soft tissue in the proximal forearm. All cases coexpressed vimentin, and one case coexpressed smooth muscle actin and desmin, resulting in a phenotype similar to that of some normal CIRCs. Although metastatic carcinoma from an occult or regressed primary tumor cannot be excluded completely, we raise the possibility of a CIRC origin for these cases.

Hurthle cell adenoma of the mediastinum: intraoperative cytology and differential diagnosis with correlative gross, histology, and ancillary studies.

A 66-year-old man was found to have a 7.5 cm mediastinal mass detected on routine chest X-rays as part of his preoperative work up for an inguinal hernia repair. An orthotopic (normally located) nongoitrous thyroid gland without evidence of connection to the mediastinal mass was also identified. The clinical differential diagnoses included lymphoma, thymoma, and germ cell tumor. Fine-needle aspiration (FNA) biopsy smears and touch imprints of the mediastinal mass showed a loosely cohesive, highly cellular population of relatively uniform cells with abundant granular cytoplasm, low nuclear to cytoplasmic (N/C) ratios, and prominent nucleoli consistent with a Hurthle cell (HC) neoplasm. Subsequently, the diagnosis of HC adenoma was confirmed on the surgically excised mediastinal mass. To the best of our knowledge, the surgical pathology and cytologic features of an HC adenoma of the mediastinum have not been reported in the literature. The gross, histologic, immunohistochemical, and electron microscopic (EM) findings, in addition to the cytologic features, are presented along with a differential diagnosis of this mediastinal neoplasm.

Amphicrine tumor.

The term amphicrine refers to cells, and tumors, which show both exocrine and endocrine features. Author s aim was to analyse the characteristics of these neoplasms. 40 suspicious cases were reviewed. Mucin-stains (PAS, diastase-PAS, Stains-all, Alcian-blue), immunohistochemistry (antibodies against Neuron-Specific Enolase (NSE), and Chromogranin A (CGA), and electronmicroscopic studies were performed to demonstrate exocrine and/or endocrine features of the tumor cells. By means of these methods, 16 cases turned out to be amphicrine tumors. Among them, there were 4 sinonasal, 1 bronchial, 1 mediastinal, 8 gastrointestinal and 2 suprarenal gland neoplasms. In connection to the subject, a brief review is given of amphicrine tumor, regarding its etiological and pathological aspects. These tumors form a distinct clinicopathological entity and should be separated from both neuroendocrine tumors and adenocarcinomas.

Primary ependymoma of the mediastinum: a clinicopathologic study of three cases.

Primary mediastinal ependymomas are unusual tumors, with only two case reports previously reported in the literature. In this study, we review our experience with three cases of primary mediastinal ependymomas, including the clinical, histopathologic, immunohistochemical, and ultrastructural features. The three patients in this study were white women with a mean age of 50 years (age range, 36 to 71 years). Presenting symptoms were nonspecific; radiographically, all lesions were circumscribed posterior mediastinal masses without evidence of bone involvement. There was no evidence of central nervous system, sacral, or pelvic ependymoma. All tumors were completely resected, ranged in size from 5 to 7 cm (mean, 6 cm), and exhibited glistening pseudocapsules. Two tumors had a solid, tan-gray cut surface and one lesion was cystic with a mural tumor nodule. All neoplasms showed histologic features of conventional cellular ependymomas with perivascular pseudorosettes and occasional true ependymal rosettes. Germ cell components were not present in any case and immunohistochemical analysis showed glial fibrillary acidic protein, S-100, and patchy cytokeratin immunoreactivity in all three cases as well as absence of reactivity for HMB 45, chromogranin, and synaptophysin. Ultrastructural features included multipart "zipper-like" junctions, intracytoplasmic lumina containing microvilli, occasional cytoplasmic basal bodies, and apical cilia. A microscopic metastasis was present in a regional lymph node in one case at the time of resection; however, there is no evidence of recurrence or distant metastasis in any of the cases during the postoperative period (mean length of follow-up, 64 months). Ependymomas rarely occur in the mediastinum and have a predilection for the posterior mediastinum. The paravertebral location, microscopic identification of adjacent sympathetic ganglia, and lack of teratomatous or other germ cell components suggest that mediastinal ependymomas are likely derived from paravertebral ependymal rests. Primary mediastinal ependymomas are characterized by a prolonged and indolent clinical course. Metastasis to regional lymph nodes may occur, but distant metastases are unusual in our experience. Complete surgical excision seems to offer the best chance for long-term survival.

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.

Endocrine characterization of primary mediastinal lymphoma.

Because of the characteristic presentation of primary mediastinal large cell lymphoma (PMLCL) in young females its known origin from thymic B-cells, there might be a role in lymphomagenesis for estrogen receptors as well as for known neuroendocrine thymic mediators. A retrospective review of all patients with diffuse large cell lymphoma seen at our institution from January 1985 to January 1994 revealed 75 consecutive cases with a diagnosis of PMLCL. Through retrieval from our pathologic archives and requests to outside pathologists, we recovered and analyzed 17 biopsy specimens for the presence of the following hormone receptors: estrogen, beta endorphin, prolactin, T3, growth hormone, and leutinizing hormone. None of the specimens stained for any of the reagents. The most plausible explanation is that PMLCL tissues are devoid of these hormonal receptors and thus these receptors do not seem to play a role in the pathogenesis of PMLCL.

Atypical glomus tumor in the mediastinum: a case report with immunohistochemical and ultrastructural studies.

A case is reported of atypical glomus tumor occurring in the posterior inferior mediastinum of a 26-year-old woman complaining of severe back pain. The tumor was composed of atypical small, round tumor cells with scattered mitotic figures. In addition to sheet-like, diffuse proliferation of the tumor cells, some areas of the tumor contained small "glomoid" cells arranged in organoid and hemangiopericytomalike patterns. Immunohistochemically, many tumor cells were positive for muscle-type actins and a few cells were focally positive for desmin. Ultrastructural studies revealed smooth muscle features of tumor cells, that is, pinocytotic vesicles, external laminas, dense plaques, and occasional thin filaments with dense bodies. The patient remained well for 5 years and 4 months after the operation without additional radiation and chemotherapy. The tumor was diagnosed as an atypical, or low-grade malignant, glomus tumor morphologically. It seems important to recognize the presence of this type of tumor in sites other than extremities and to differentiate it from other malignant small, round cell tumors.

[Study on ultrastructure morphology of fine needle aspiration of mediastinal and lung lesions].

Specimens of Mediastinal lesions and lung masses collected by fine needle aspiration (FNA) was examined with both light and transmission electron microscopy. Sixty eight specimens (9 mediastinal and 40 lung masses, 4 metastatic chest masses and 15 metastatic lymph nodes from lung cancer) from 104 cases (60.5%) were satisfactory for evaluation. With light microscopy, the nature of the lesions was assessed and the ultrastructural features of the lesions were evaluated with transmission electron microscopy. Diagnosis of histologic type of the lesions by light microscopy was consistent with that by transmission electron microscopy at a conformity rate of 50.4%. The results indicate that ultrastructural features are valuable in ascertaining histologic type of the lesions.

Chordomas of the mediastinum: clinicopathologic, immunohistochemical, and ultrastructural study of six cases presenting as posterior mediastinal masses.

Six cases of chordomas presenting as primary posterior mediastinal tumors are described. Three patients were female, and three were male between the ages of 8 and 65 years (mean, 40.6 years). In all cases, the tumors presented radiographically as relatively well-circumscribed, encapsulated soft tissue masses that did not seem to be related to the thoracic or dorsal spine. Only in one case, focal infiltration of bone at the level of T6-T7 was observed at the time of surgery. Histologically, the lesions showed a spectrum of features that ranged from sheets and cords of large cells with abundant vacuolated cytoplasm to small, stellate cells embedded within an abundant mucoid matrix. In one case, the cell population showed more pronounced nuclear atypia with loss of cytoplasmic vacuolization, frequent mitotic figures, necrosis, and solid areas characterized by a perivascular distribution of atypical spindle cells set against a myxoid stroma. Another case showed features of chondroid chordoma, with an immature chondroid-appearing matrix surrounding the atypical tumor cells. Immunohistochemical studies in all cases showed positive staining of the tumor cells with CAM 5.2 and broad-spectrum keratin, epithelial membrane antigen (EMA) and vimentin, and, to a lesser extent, with S-100 protein. Stains for muscle actin, carcinoembryonic antigen (CEA), and desmin were negative. Ultrastructural examination in two cases showed a spectrum of features that varied from large cells with abundant cytoplasm containing scattered ribosomes, glycogen granules, Golgi apparatti, abundant intermediate filaments, and small lumen formation with immature microvilli to smaller cells with elongated cytoplasmic processes, fewer intermediate filaments, rare desmosome type intercellular junctions, and complexes of mitochondria/rough endoplasmic reticulum. On clinical follow-up, two patients died with metastases to the lungs, chest wall, and liver from 1 to 3 years after diagnosis, and two patients are alive and well without evidence of disease after 3 and 16 years. Chordoma should be entertained in the differential diagnosis of posterior mediastinal tumors. Application of immunohistochemical stains or electron microscopy will be of aid in separating them from other conditions that may histologically closely resemble these lesions.

Neuroblastoma of the anterior mediastinum in an 80-year-old woman.

A 7-cm anterior mediastinal tumor in an 80-year-old woman was found by light and electron microscopy to be a neuroblastoma. Immunoreactivity for neuron-specific enolase, synaptophysin, and chromogranin supported the diagnosis. Neuroblastoma is an uncommon tumor in adults and we are not aware of a previous report of such a tumor in a patient of this age.

Melanotic paraganglioma of the posterior mediastinum.

A melanotic paraganglioma occurred in a 57-year-old woman, located in the left paravertebral space of the upper mediastinum. It was totally resected. During a 5 year follow up period neither tumour recurrence nor metastasis were observed. Histological examination of the tumour revealed a paraganglioma with monomorphous chief cell like elements which were arranged in a "zellballen" pattern. Immunohistochemical results also were in accordance with the diagnosis since neuron-specific enolase, chromogranin and synaptophysin were found in tumour cells whereas keratin was not. Additionally, neurosecretory granules were found in tumour cells during electron microscopy. A peculiar feature of the tumour was its strong pigmentation due to melanin located within the tumour cells and tumour associated melanophages. The simultaneous expression of functional properties of two different neural crest derived cells in one tumour stresses the close relationship between all neural crest elements and is in accordance with the observation of other melanotic, non-melanomatous tumours.

Mesothelial cell inclusions within mediastinal lymph nodes.

The presence of mesothelial cell inclusions within mediastinal lymph nodes is an extremely rare occurrence with apparently only two previously reported cases. We report a single case with immunohistochemistry and transmission electron microscopy. A study of 318 mediastinal nodes from 80 patients using haematoxylin and eosin and immunohistochemistry is reported with the observation of no further positive cases. A review of the literature concerning nodal inclusions found at other anatomical sites aids discussion on the aetiology of this type of nodal inclusion.

Malignant smooth muscle tumors presenting as mediastinal soft tissue masses. A clinicopathologic study of 10 cases.

BACKGROUND: Smooth muscle tumors presenting as mediastinal soft tissue masses are extremely rare and often are mistaken for other neoplastic conditions. METHODS: Ten cases of patients with malignant smooth muscle tumors presenting as mediastinal soft tissue masses were studied and correlated with their clinical behavior. Tissues were examined histologically and with immunohistochemical stains in all cases, and by electron microscopy in two cases. RESULTS: The patients' ages ranged from 26 to 71 years (mean, 56 years); three were women, and seven were men. Three cases were located in the anterior mediastinum and seven in the posterior mediastinum. The patients with anterosuperior mediastinal tumors all presented with signs and symptoms referable to their lesions; the patients with posterior mediastinal masses (with the exception of one) were all asymptomatic. Grossly, the lesions were well circumscribed and unencapsulated, ranging from 6 to 18 cm in greatest dimension and showed a homogeneous, rubbery cut surface with prominent cystic and myxoid areas. The tumors in all patients appeared to arise from the soft tissues within the mediastinum and were unrelated to adjacent structures. In three patients, the tumors compressed and displaced the esophagus without infiltrating its wall, and in one patient, the tumor was found in close proximity, although unattached, to a large vessel. Histologically, the lesions exhibited a spectrum of morphologic appearances that ranged from low grade leiomyosarcoma with mild-to-moderate nuclear atypia and low mitotic activity (< 3/10 high power fields [HPFs]), to high grade tumors with marked nuclear pleomorphism, extensive areas of necrosis, and high mitotic activity (> 10 mitoses/10 HPFs). One case was characterized by a striking epithelioid morphology with large, round cells arranged in small clusters; another was associated with an incidental microscopic focus of thymic seminoma in the adjacent thymus. Immunohistochemical stains in all cases showed positive labeling of the tumor cells with smooth muscle actin, desmin, and vimentin antibodies. Electron microscopy in two cases showed features of smooth muscle differentiation, i.e., spindle cells surrounded by basal lamina material, immature cell junctions, and abundant intracytoplasmic filaments with focal condensations. All patients were treated with surgical excision. On follow-up, three patients with Stage IIIb and IVa tumors died 2-7 years after surgery, and two patients with Stage Ib and IIb were alive and well 4 and 6 years after surgery, respectively. CONCLUSION: Leiomyosarcomas may arise as primary tumors originating from mediastinal soft tissues in both anterior and posterior compartments. Because of their large size and frequent areas of cystic and myxoid degeneration, they may be confused histologically with neural or other neoplasms. As with their counterparts in other soft tissue locations, histologic grade and clinical stage are the most useful parameters for assessing prognosis.

Epithelioid hemangioendothelioma of the anterior mediastinum. Clinicopathologic, immunohistochemical, and ultrastructural analysis of 12 cases.

Twelve cases are reported of primary epithelioid hemangioendothelioma of the anterior mediastinum. Patient ages ranged from 19 to 62 years (mean, 49.4); three were women and nine were men. Seven patients presented with symptoms due to compression of surrounding structures; the remainder were asymptomatic and the lesions were discovered on routine chest x-ray films. The tumors measured from 4.5 to 13.5 cm in greatest diameter; they were encapsulated and well-circumscribed in seven cases and locally infiltrative in five. Histologically, a spectrum of features was observed ranging from those classically described for low-grade epithelioid hemangioendothelioma at other locations--including cells with abundant eosinophilic cytoplasm showing prominent vacuolization and intracellular lumen formation, few mitotic figures, and myxoid changes in the stroma--to more pronounced cytologic atypia, increased mitotic activity, and areas of necrosis. Metaplastic bone formation and osteoclast-type giant cells were observed in five cases, and four tumors displayed focally a prominent intravascular papillary endothelial component. Immunohistochemical studies showed positive staining of the neoplastic cells with factor VIII-related antigen and vimentin and focal staining in most cases with Ulex europaeus lectin. Stains for broad-spectrum keratin, CAM-5.2, S-100 protein, CD34, actin, and desmin were negative. Electron microscopic examination in three cases showed features distinctive for epithelioid vascular endothelial cells, including abundant cytoplasmic intermediate filaments, basal lamina material, marked pinocytotic activity, and primitive intracytoplasmic lumen formation. All cases were treated by surgical excision. Follow-up information was available in nine patients; seven patients were alive and well without evidence of disease 2-21 years after diagnosis (mean follow-up, 8 years); one patient had a recurrence after 1 year and died due to complications of surgery, and another patient died after 1 year of undetermined causes. Despite their often ominous clinical, radiological, and pathological features, epithelioid hemangioendotheliomas arising in the anterior mediastinum appear to behave as low-grade malignant neoplasms that may be adequately controlled in most instances by surgery alone.