Both serum and tissue Galectin-1 levels are associated with adverse clinical features in neuroblastoma.

BACKGROUND: Neuroblastoma is one of the most common pediatric solid tumors. Although the 5-year overall survival rate has increased over the past few decades, high-risk patients still have a poor prognosis due to a lack of biomonitoring therapy. This study was performed to investigate the role of Galectin-1 in neuroblastoma biomonitoring therapy. PROCEDURE: A tissue microarray containing 37 neuroblastoma tissue samples was used to evaluate the correlation between Galectin-1 expression and clinical features. Blood samples were examined to better understand whether serum Galectin-1 (sGalectin-1) could be used for biomonitoring therapy. Kaplan-Meier analysis and ROC analysis was conducted to distinguish the outcome associated with high or low expression of Galectin-1 in patients with neuroblastoma. RESULTS: Increased Galectin-1 expression was found in neuroblastoma and it was further demonstrated that elevated tissue Galectin-1 expression was related to INSS stage, histology, bone marrow metastasis, and poor survival. sGalectin-1 levels were higher in newly diagnosed patients with neuroblastoma than healthy subjects. Patients with elevated sGalectin-1 through treatment cycles correlated with the poor chemo-responses and tended to have worse outcomes, such as metastasis or stable tumor size, whereas gradually decreasing sGalectin-1 levels correlated with no observed progression in clinical symptoms. CONCLUSIONS: Tissue and serum Galectin-1 levels were associated with adverse clinical features in patients with neuroblastoma, and sGalectin-1 could be a potential biomarker for monitoring therapy.

Soft tissue metastasis of mediastinal non-functioning paraganglioma with unusual TTF-1 expression: a potential diagnostic pitfall.

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary.

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

Anterior mediastinal neuroblastoma in an adult: an additional case of a rare tumor in an unusual location with review of the literature.

Neuroblastoma is rare in the adult population, especially in thoracic or mediastinal locations, with only 25 previously reported cases. We report an additional example of primary thymic neuroblastoma in a previously asymptomatic 71-year-old man with an anterior mediastinal mass who underwent robotic excision with pericardium and adjacent lung. The tumor was a 5.2 cm partially encapsulated, white-tan and rubbery mass with grossly identifiable areas of necrosis (25%) and hemorrhage. Histologically, the specimen showed a rim of adipose tissue and residual thymic tissue with areas of cystic thymic epithelium and prominent lymphoid tissue containing Hassall's corpuscles. The tumor was composed of uniform, round cells with scant cytoplasm and small nuclei with inconspicuous nucleoli set within a background of conspicuous neuropil. Mitotic figures were easily found. By immunohistochemistry, the tumor cells expressed synaptophysin, chromogranin, NKX2.2 (diffuse, nuclear), GFAP (patchy), SMI31 (neurofilament) (focal, cytoplasmic), and TdT (diffuse, nuclear), while lacking expression of CD99, TTF-1, CK 20, MCPyV, PHOX2B, Olig2, OCT3/4, CD45, CD3 and PAX5. S100 protein was negative in the neuroblastic cells, with scattered positive cells in a vague sustentacular-like pattern. Fluorescence in situ hybridization for isochromosome 12p and EWSR1 gene rearrangement were negative. As thymic neuroblastoma is extremely rare in adults, a neuroblastic tumor of germ cell origin (either primary or metastatic) or spread from a sinonasal tract tumor should be excluded because of differing treatments and prognoses. The properties of these rare neoplasms appear similar to olfactory neuroblastoma rather than pediatric-type neuroblastoma.

Angiomatoid fibrous histiocytoma: unusual sites and unusual morphology.

Angiomatoid fibrous histiocytoma is a soft tissue neoplasm of low malignant potential, typically occurring in the superficial soft tissues of the extremities in children and young adults. Occurrence outside somatic soft tissues is most uncommon. This report describes eight such cases, involving the lung (three cases), mediastinum (one case), vulva (two cases), retroperitoneum (one case) and ovary (one case), with the latter three locations being hitherto unreported sites of occurrence. Patients had a median age of 48 years, and presented with symptoms related to the mass lesion (five cases) or were incidentally found to harbor a tumor (three cases). Besides the typical histological features such as an outer shell of lymphoid tissue, multinodular aggregates of dendritic-like tumor cells, blood-filled spaces and abundant admixed plasma cells, unusual features were found focally in some cases, including clear cells, rhabdomyoblast-like cells, pulmonary edema-like pattern and tumor cell cords lying in a myxoid stroma. Immunoreactivity for the epithelial membrane antigen, desmin, smooth-muscle actin, CD68 and CD99 was found in 100, 63, 43, 100 and 100% of cases, respectively. Molecular studies provided support for the diagnosis in all seven tested cases-EWS gene translocation in six cases (partner gene being CREB1 in three and ATF1 in two in which information was available) and FUS gene translocation in one case. Comparison of the reported cases of extrasomatic angiomatoid fibrous histiocytoma with their somatic soft tissue counterparts showed a number of differences: higher mean age, slight male predominance (particularly for bone lesions), larger tumors, higher frequency of systemic symptoms, higher recurrence rate, myxoid change being more common and a much higher frequency of EWS/ATF1 gene fusion.

Primary mediastinal seminoma with florid follicular lymphoid hyperplasia: a case report and review of the literature.

BACKGROUND: First described in 1955 Primary mediastinal seminomas are rare. Only 1-4% of mediastinal tumours are germ cell tumors; majority of which are teratomas. They typically present in men aged between 20 and 40 years. Very few cases are reported in the literature. Florid follicular lymphoid hyperplasia can obscure the malignant cells and is a rarer finding still. We present a rare case of a 48 year old man with a primary mediastinal seminoma with florid follicular lymphoid hyperplasia; found following excision of a clinically presumed thymoma. CASE PRESENTATION: A 48 year old man was referred for excision of a thymic mass. The presumed diagnosis was a thymoma; following preoperative investigations. The mass was incidentally found on a radiological imaging. However, the patient did report mid-sternal discomfort on lying flat and breathlessness. The patient underwent a thymectomy via a partial median sternotomy with good recovery. Histological assessment was that the mass was in fact a primary mediastinal seminoma with florid follicular lymphoid hyperplasia. A primary testicular malignancy was excluded and the patient required no further oncological treatment. CONCLUSIONS: Only 11 cases have previously been reported of primary mediastinal seminoma with florid follicular lymphoid hyperplasia. Although rare, a primary mediastinal seminoma should be considered as a differential diagnosis for presentations with a thymic mass. Tumour markers can be helpful, however are only positive in third of cases. Ultrasound imaging of the gonads is essential to exclude a primary gonadal lesion. Pure seminomas are radiotherapy and chemotherapy sensitive however the mainstay treatment of primary mediastinal seminomas remains surgical excision. Radiotherapy is reserved postoperatively for incomplete surgical margins.

A multilocular thymic cyst associated with mediastinal seminoma: evidence for its medullary epithelial origin highlighted by POU2F3-positive thymic tuft cells and concomitant myoid cell proliferation.

Multilocular thymic cyst (MTC) and germ cell tumors are common diseases that impact the mediastinum. Correctly diagnosing these diseases can be difficult because several other conditions can mimic them. We report a male patient with MTC associated with mediastinal seminoma. A needle biopsy of the mediastinal tumor revealed numerous epithelioid cell granulomas that mimicked sarcoidosis or mycobacterial infection. However, large atypical cells positive for Oct3/4 and KIT were noted between the granulomas; thus, we diagnosed the patient with mediastinal seminoma. The resected tumor, after chemotherapy, consisted of multiple cystic lesions, and a residual germ cell tumor was first considered. However, thymic medulla-specific elements, namely, POU2F3-positive thymic tuft cells and rhabdomyomatous myoid cells accompanying the epithelium, led to the correct diagnosis of MTC. Our case underscores the importance of recognizing the histological features associated with mediastinal seminoma and provides novel findings for MTC pathogenesis, namely, the presence of thymic tuft cells.

Vasculogenic Mesenchymal Tumor: A Clinicopathologic and Molecular Study of 55 Cases of a Distinctive Neoplasm Originating From Mediastinal Yolk Sac Tumor and an Occasional Precursor to Angiosarcoma.

We report 55 postchemotherapy resections of primary nonseminomatous mediastinal germ cell tumors with prominent vasculogenic features showing the formation of rudimentary to well-developed neoplastic vessels within primitive mesenchyme. These cases represented 25% of a cohort of 221 such specimens. The patients were 19 to 49 years old (mean, 28 y) and 98% had serological evidence of yolk sac tumor. The vasculogenic lesions, felt to represent a neoplastic reiteration of embryonic vasculogenesis in the splanchnic mesoderm of the yolk sac, were further subdivided into teratoma with vasculogenic stroma (n=9), vasculogenic mesenchymal tumor (VMT) (n=42, further classified into low grade [n=24] and high grade [n=18]), and angiosarcoma (n=4). The distinction of teratoma with vasculogenic stroma from VMT was based solely on the greater extent of VMT (exceeding 1 low power [×4 objective] microscopic field), with both categories showing a spectrum of vessels lined by atypical endothelium in a nonendothelial neoplastic stroma that often also generated vascular walls comprised of atypical smooth muscle. The angiosarcomas showed stratification of highly atypical endothelial cells or anastomosing vessels lined by nonstratified but cytologically similar endothelium. Immunohistochemical studies supported the generation of neoplastic vessels from the tumor stroma, most commonly by the development of stromal clefts showing reactivity for podoplanin, CD34, and occasionally ERG, followed by the gradual development from the clefts of thin-walled vessels that later became encircled by stromal cells showing smooth muscle differentiation by immunohistochemistry. Occasionally, round collections of stromal erythrocytes became surrounded by stromal cells to generate blood vessels. Fluorescence in situ hybridization showed chromosome 12p copy number increase in both the endothelial component and stromal component in 8/9 VMT cases and in 1/1 angiosarcoma. On follow-up, no patient with teratoma with vasculogenic stroma had evidence of a subsequent vascular tumor or sarcoma, whereas 8 of the 35 (23%) patients with VMTs (2 low grade and 6 high grade) and meaningful follow-up developed sarcoma (1 angiosarcoma, 2 rhabdomyosarcomas, and 5 not further characterized). The difference between low-grade and high-grade tumors was of borderline significance (P=0.058). Two of the 4 patients with angiosarcoma died of metastatic angiosarcoma, with the other 2 disease-free at 6.8 and 7 years. Compared with the 165 patients with follow-up and no vasculogenic lesions, there was a highly significant (P=4.3×10-5) association of any vasculogenic lesion with sarcomatoid tumors during the clinical course of VMT patients. In addition, 5/46 patients with follow-up and vasculogenic lesions (11%) died of either leukemia or myelodysplastic syndrome compared with 2 of 166 (1%) lacking them (P=0.0012). Three of the 5 patients had identifiable immature hematopoietic cells within their vasculogenic lesions, but 4 other VMT patients with these did not develop leukemia or myelodysplasia. We conclude: (1) vasculogenic lesions are frequent in postchemotherapy resections of primary mediastinal germ cell tumors with yolk sac tumor components; (2) they mostly consist of neoplastic vessels in a stroma that also generates neoplastic vascular walls of smooth muscle; (3) VMTs are associated with an increased incidence of sarcomas, even though most vasculogenic lesions in this context do not meet criteria for angiosarcoma; (4) the presence of vasculogenic lesions in postchemotherapy resections of primary mediastinal germ cell tumors place patients at increased risk for leukemia or myelodysplasia.

Relapse with malignant transformation after chemotherapy for primary mediastinal seminoma: case report.

This case report details a relapse with malignant transformation after the completion of bleomycin, etoposide and cisplatin chemotherapy for primary mediastinal seminoma, although the residual mass after chemotherapy was <3 cm in size and did not display an increased uptake of fluorodeoxyglucose when examined using positron emission tomography.

Water-Clear Cell Adenoma of the Mediastinal Parathyroid Gland.

Water-clear cell adenoma of the parathyroid gland is a rare neoplasm that consists of cells with abundant clear-pink cytoplasm. There have only been 19 cases reported in the English literature. Here we report a case of water-clear cell adenoma of the mediastinal parathyroid gland. A 70-year-old male patient presented to the hospital with back pain and a mediastinal mass 6 cm in size was detected. After excision and microscopic evaluation, uniform, large clear cells with fine cytoplasmic vacuolization, without nuclear atypia, and arranged in solid and acinar patterns were revealed. The cells formed nests that were separated by fine fibrovascular septae and stained positively with anti-parathyroid hormone. To the best of our knowledge, this has not been previously reported in this location. In the differential diagnosis of clear cell lesions of the mediastinum, water-clear cell parathyroid adenoma should be considered.

Mucinous adenocarcinomas of the thymus: report of 2 cases and review of the literature.

BACKGROUND: Most adenocarcinomas of the mediastinum are metastatic lesions. Primary thymic adenocarcinomas are extremely rare neoplasms. We could find only 12 cases reported in the literature; of these 12, only 4 were of the mucinous subtype. DESIGN: We report 2 additional cases of the mucinous subtype, including a previously unreported mucinous variant with numerous psammoma bodies. RESULTS: The first case in a 61-year-old woman resembled a mucinous (colloid) carcinoma of other organs such as the breast and colon. It consisted of islands and strips of tumor cells floating in large pools of extracellular mucin. A unique feature of this tumor was the presence of numerous psammoma bodies. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7 and negative for CD5. The second case in an 82-year-old woman was a mucinous adenocarcinoma arising from a thymic cyst with areas of transition from benign to dysplastic epithelium. The tumor cells formed dilated glands, cords, and small nests that infiltrated the thymic cyst wall and exhibited evidence of mucin production. Immunohistochemically, the tumor cells were positive for CK 7 and focally positive for both CD5 and CK 5/6. CONCLUSIONS: Mucinous adenocarcinoma, with or without, psammoma bodies, may be of primary thymic origin and should be considered in the differential diagnosis of malignant mediastinal tumors. These 2 cases provide further documentation of the rare occurrence of primary mucinous adenocarcinomas of the thymic gland.

Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases.

The clinicopathologic features of 46 patients with germ cell tumors with sarcomatous components (GCTSC) involving either the primary site or their metastases were studied. There were 43 men and 3 women aged 17 to 74 years. Twenty-three tumors arose in the mediastinum, 2 in the retroperitoneum, and 21 in the gonads. The germ cell component consisted of pure mature or immature teratoma (23 cases), teratoma mixed with other seminomatous or nonseminomatous components (17), pure seminoma (2), intratubular germ cell neoplasia (1), and yolk sac tumor (1). The SC included embryonal rhabdomyosarcoma (29), angiosarcoma (6), leiomyosarcoma (4), undifferentiated sarcoma (3), myxoid liposarcoma (1), malignant peripheral nerve sheath tumor (1), malignant "triton" tumor (1), and epithelioid hemangioendothelioma (1). Immunohistochemical studies were carried out in 34 cases with appropriate results supporting the diagnoses. Metastases containing both GCT and SC were observed in 6 cases, metastases of SC alone in 4, and metastases containing only GCT elements in 3. All patients were treated by cisplatinum-based chemotherapy plus other agents followed by surgery. Clinical follow-up was available in 40 patients (1 to 96 mo; mean=24 mo). Thirty-two of 40 patients either died of tumor (25/40; 62.5%) or were alive with advanced, progressive disease (7/40; 17.5%), and only 8/40 (20%) were alive and free of disease between 5 to 40 months (mean=18 mo). Comparison of these patients with an age-matched and stage-matched control group of patients with GCT without SC showed statistically significant differences in survival between the 2 cohorts (P

Mediastinal lymphangiomatosis coexisting with occult thymic carcinoma.

Mediastinal lymphangiomatosis in a 70-year-old woman was diagnosed on a medical checkup. The tumor was resistant to sclerotherapy with OK432 or bleomycin. The patient continued on a downhill course and died approximately 3 years after the initial diagnosis. Autopsy revealed a large tumor mass occupying the anterior mediastinum and firmly adhered to the pericardium and the pleura. The tumor consisted of two intermingled lesions: dilated vessels lined with D2-40-positive lymphatic endothelium and CD5-positive atypical cell nests with focal keratinization. The former was diagnosed as lymphangiomatosis and the latter as thymic squamous cell carcinoma. Vascular endothelial growth factor (VEGF)-C, a growth factor for lymphatic endothelial cells, was expressed by the carcinoma, and VEGF-C receptor was expressed by the endothelium of lymphangiomatosis. These findings suggested that VEGF-C derived from the thymic carcinoma induced the lymphangiomatosis lesion in a paracrine manner.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas.

Giant Leiomyoma Arising from the Mediastinal Pleura: A Case Report.

This report presents a rare case involving a patient with a giant leiomyoma originating from the mediastinal pleura. The patient underwent a medical examination, and chest radiography revealed a giant tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a well demarcated, heterogeneous mass which seemed to originate from the posterior mediastinum. Positron emission tomography (PET) showed the uptake of this tumor with a standardized uptake value of 4.9. We suspected that this tumor was a solitary fibrous tumor, and the patient underwent a surgical resection. Intraoperative exploration revealed a well-encapsulated tumor measuring 15 × 11 cm that appeared to originate from the mediastinal pleura. Immunohistochemical findings revealed a benign leiomyoma. We finally diagnosed the patient with a mediastinal leiomyoma. The present report describes CT, MRI, and PET findings of leiomyoma, and presents a review of relevant literature.

Cystic well-differentiated neuroendocrine carcinoma (carcinoid tumor): a clinicopathologic and immunohistochemical study of two cases.

Two cases of primary neuroendocrine carcinoma (carcinoid tumor) arising in the walls of a multilocular thymic cyst (MTC) are described. The patients were 2 men, ages 36 and 44 years. Clinically, the patients had chest pain, cough, and dyspnea. Radiographic evaluation demonstrated the presence of anterior mediastinal tumor in both patients, and complete surgical resection of the tumor mass was performed. The tumors measured approximately 6 and 8 cm in greatest dimension and were cystic with solid areas but did not show areas of necrosis or hemorrhage. Histologic examination revealed a cystic tumor with features similar to those previously described for MTCs. In addition, in the walls of the cystic structures, there was cellular proliferation arranged in a nesting growth pattern, similar to the more solid areas of the tumor. The tumor was characterized by a homogenous cellular proliferation with mild cellular atypia and no more than 2 mitotic figures per 10 high-power fields. Immunohistochemically, the tumor cells showed strong positive reactions for keratin and neuroendocrine markers, ie, chromogranin and synaptophysin. Both patients were alive after periods of 12 and 18 months.

Mediastinal rhabdomyoma: case report and review of the literature.

Rhabdomyomas are benign tumors in which at least some cells are differentiated as skeletal muscle cells with cytoplasmic cross-striations. Extracardiac adult rhabdomyoma is an extremely uncommon benign neoplasm that usually involves the head and neck region. Rare cases have been reported to involve other sites of the body including mediastinum. We report the fourth case of mediastinal adult rhabdomyoma.

Expression pattern of intracellular leukocyte-associated proteins in primary mediastinal B cell lymphoma.

Two microarray studies of mediastinal B cell lymphoma have shown that this disease has a distinct gene expression profile, and also that this is closest to the pattern seen in classical Hodgkin's disease. We reported previously an immunohistologic study in which the loss of intracellular B cell-associated signaling molecules in Reed-Sternberg cells was demonstrated, and in this study we have investigated the expression of the same components in more than 60 mediastinal B cell lymphomas. We report that these signaling molecules are frequently present, and in particular that Syk, BLNK and PLC-gamma2 (absent from Reed-Sternberg cells) are present in the majority of mediastinal B cell lymphomas. The overall pattern of B cell signaling molecules in this disease is therefore closer to that of diffuse large B cell lymphoma than to Hodgkin's disease, and is consistent with a common cell of origin as an explanation of the similar gene expression profiles.