Analysis of the inflammatory tumor microenvironment in meningeal neoplasms.

BACKGROUND: Properties of the inflammatory tumor microenvironment are associated with disease subtype, grade, and prognosis in various cancer entities. As immune-modulatory therapies are currently being explored in patients with meningeal neoplasms, we investigated their inflammatory microenvironment (meningiomas and solitary fibrous tumor/hemangiopericytoma (SFT/HPC)). MATERIALS AND METHODS: 74 meningeal tumor specimens: (10/74 (13.5%) atypical meningioma; 8/74 (10.8%) anaplastic meningioma; 8/74 (10.8%) chordoid meningioma; 9/74 (12.2%) fibroblastic meningioma; 10/74 (13.5%) transitional meningioma; 3/74 (4.1%) rhabdoid meningioma; 7/74 (9.5%) meningothelial meningioma; SFT/HPC (19/74 (25.7%) were retrieved from the Neuro-Biobank, Medical University of Vienna, Austria. RESULTS: Tumor-infiltrating lymphocyte (TIL) infiltration could be observed in the majority of the investigated specimens (CD3+: 66/74 (89.2%); CD8+: 47/74 (63.5%); CD45RO+: 29/73 (39.2%); FOXP3+ 19/74 (25.7%); PD1+: 3/74 (4.1%). No difference in TIL infiltration was observed between SFT/HPC and meningioma cases. Higher density of FOXP3+ TILs was observed with increasing WHO grade in meningioma specimens (p = 0.005). Membranous programmed cell death ligand 1 (PD-L1) expression was observed in 4/74 (5.4%) specimens, with 3/74 (4.1%) presenting with 1% and 1/74 (1.4%) with 3% PD-L1 expressing tumor cells. Lymphatic vessels as identified by podoplanin immunohistochemistry were observed in 10/74 (13.5%) specimens and were significantly associated with presence of membranous PD-L1 expression on tumor cells (p = 0.003). CONCLUSION: Infiltration by various TIL subtypes can be observed in the majority of meningeal neoplasms, with enrichment of FOXP3-positive regulatory T-cells in higher-grade meningioma. PD-L1 expression on tumor cells was only infrequently found. A better understanding of the pathobiological role of the immune system in meningeal neoplasms may facilitate development of immunomodulatory treatment approaches in meningeal tumors.

CD34 + tumours of the orbit including solitary fibrous tumours: a six-case series.

BACKGROUND: To report six cases of CD34+ fibroblastic mesenchymal tumours, which are uncommon neoplasms in the orbit. CASE PRESENTATION: Six patients presenting with proptosis and palpable mass who were later diagnosed with fibrous solitary tumours, fibrous histocytoma or haemangiopericytoma in the orbit were included. All patients received radiologic examinations and surgical excision for histopathology and immunohistochemistry examinations. Five patients had no recurrence after a minimum follow-up of 12 months. One patient (case 6) experienced recurrence twice, and had debulking surgeries each time. At present, the patient still has remnant tumour in the orbit, but no growth has been detected during the past two years. The tumour size will be closely monitored. CONCLUSIONS: Even though fibroblastic tumours are rarely found in the orbit, they can present as a palpable mass with proptosis. Complete surgical excision is important for long-term prognosis, and immunohistochemical study is helpful for confirming pathologic diagnosis.

The pericyte antigen RGS5 in perivascular soft tissue tumors.

Perivascular soft tissue tumors are relatively uncommon neoplasms of unclear lineage of differentiation, although most are presumed to originate from or differentiate to pericytes or a modified perivascular cell. Among these, glomus tumor, myopericytoma, and angioleiomyoma share a spectrum of histologic findings and a perivascular growth pattern. In contrast, solitary fibrous tumor was once hypothesized to have pericytic differentiation--although little bona fide evidence of pericytic differentiation exists. Likewise the perivascular epithelioid cell tumor (PEComa) family shares a perivascular growth pattern, but with distinctive dual myoid-melanocytic differentiation. RGS5, regulator of G-protein signaling 5, is a novel pericyte antigen with increasing use in animal models. Here, we describe the immunohistochemical expression patterns of RGS5 across perivascular soft tissue tumors, including glomus tumor (n = 6), malignant glomus tumor (n = 4), myopericytoma (n = 3), angioleiomyoma (n = 9), myofibroma (n = 4), solitary fibrous tumor (n = 10), and PEComa (n = 19). Immunohistochemical staining and semi-quantification was performed, and compared to αSMA (smooth muscle actin) expression. Results showed that glomus tumor (including malignant glomus tumor), myopericytoma, and angioleiomyoma shared a similar diffuse immunoreactivity for RGS5 and αSMA across all tumors examined. In contrast, myofibroma, solitary fibrous tumor and PEComa showed predominantly focal to absent RGS5 immunoreactivity. These findings further support a common pericytic lineage of differentiation in glomus tumors, myopericytoma and angioleiomyoma. The pericyte marker RGS5 may be of future clinical utility for the evaluation of pericytic differentiation in soft tissue tumors.

Orbital solitary fibrous tumor: encompassing terminology for hemangiopericytoma, giant cell angiofibroma, and fibrous histiocytoma of the orbit: reappraisal of 41 cases.

Hemangiopericytomas and solitary fibrous tumors are uncommon neoplasms found in many locations, including the orbit. Both mesenchymal neoplasms share several clinicopathologic features, thus prompting intense debate as to whether they are variants of the same entity or merit separate designations in the orbit. These 2 entities, with the addition of giant cell angiofibroma of orbit, are of benign- to uncertain-behavior, CD34-positive, collagen-rich, specialized fibroblastic tumors, which may have overlapping or histologically identical features. In addition, so-called fibrous histiocytoma of orbit, a previous designation, has overlapping morphologic features with these tumors. To date, a large series of these collagen-rich fibroblastic tumors of the orbit has not been fully explored. Forty-one fibroblastic orbital tumors, originally diagnosed as hemangiopericytomas (n = 16), fibrous histiocytomas (n = 9), mixed tumors (hemangiopericytomas/fibrous histiocytoma) (n = 14), and giant cell angiofibromas of orbit (n = 2) between 1970 and 2009, were retrieved from our consultation files, the Ophthalmic Registry, at the Armed Forces Institute of Pathology. Slides and clinical records were reviewed, analyzed, and compared. Immunochemistry was performed for CD34, CD99, Bcl-2, Ki-67, and p53. Upon histologic review, all cases were reclassified as solitary fibrous tumor (41/41). The patients included 23 (56%) males, 17 (41%) females, and 1 unknown, with a mean age at presentation of 40.7 years (range, 16-70 years). The sites of involvement were the right orbit in 18 (44%) cases and the left in 16 (39%) cases. Tumors ranged in size from 0.4 to 5.0 cm (mean, 2.2 cm). Seventeen (41%) patients presented with an orbital mass, 8 (20%) with proptosis, 2 (5%) with painful mass, and 2 (5%) with painless mass. Duration of symptoms ranged from 3 to 96 months, with a mean of 23 months (median, 9 months). Microscopically, all lesions showed considerable similarity, varying in degree of cellularity, stromal collagen, and the presence of giant cells. Overlapping features with soft tissue giant cell fibroblastoma were observed. Immunochemistry revealed positivity for CD34 in all cases (100%), p53 in 85%, CD99 in 67.5%, and Bcl-2 in 47.5%. Although Ki-67 labeling was seen in all cases, it ranged from less than 1% in 54.3% of cases to 5% to 10% in 20% of cases. Taken together, the findings of this study suggest that orbital hemangiopericytoma and some cases previously designated as fibrous histiocytoma, giant cell angiofibroma of orbit, and solitary fibrous tumor have overlapping morphologic and immunohistochemical features and should be designated as solitary fibrous tumor. Adipocytes and unusual multivacuolated adipocytic cells may be present in these tumors, as well stromal myxoid change; and even stromal intramembranous ossification can be observed. There are overlapping features of orbital solitary fibrous tumor with another CD34-positive specialized fibroblastic tumor of soft tissue, giant cell fibroblastoma. Morphologic criteria for uncertain behavior to low-grade malignant ocular solitary fibrous tumors can be made by cytologic atypia and increased mitotic activity, but overall outcome for malignant solitary fibrous tumors of the eye should be further explored.

Hemangiopericitoma da mama / Hemangiopericytoma of the breast

Hemangiopericitoma é uma incomum neoplasia mesenquimal, ricamente vascularizada, compostapor células indiferenciadas, descrita em várias localizações do corpo humano e raramente namama. Na maioria dos casos, possui comportamento biológico benigno. Relata-se um caso de hemangiopericitomade mama feminina, enfatizando aspectos clínicos e anatomopatológicos típicosdesta neoplasia.

Hemangiopericytoma is an uncommon richly vascular mesenchymal neoplasm, composed of undifferentiatedcells that has been described in various sites of the human body, but only rarely in the breast. Themajority of cases has a benign biological behavior. We report one case of hemangiopericytoma of femalebreast emphasizing typical clinical and anatomopathological features of this neoplasm.

Solitary fibrous tumor of the parapharyngeal space.

Solitary fibrous tumors are benign neoplasms of mesenchymal origin. They usually arise from the visceral or parietal pleura and peritoneum, although they have been found in many areas throughout the body. We report a case of solitary fibrous tumor of the parapharyngeal space. Microscopically, the tumor contained spindle cells with areas of marked hypercellularity without a definitepattern. Consistent with a benign lesion, there were few mitoses and no necrosis. The tumor cells stained strongly positive for CD34 and vimentin. At the 2-year follow-up, the patient was well and free of local and/or distant disease.

Sinonasal haemangiopericytoma: a case report.

Haemangiopericytoma (HPC) is a rare vascular tumour that is thought to originate from the vascular pericytes of Zimmerman. HPC may arise in any part of the body, and from 15 to 30% of these tumours are found in the head and neck, with a rare involvement of the sinonasal region The main symptoms of nasal HPC, epistaxis and nasal obstruction, are not typical. The final diagnosis is based on the histopathology and immunochemistry, and whether the tumour is benign or malignant is defined on the basis of the clinical history. HPC located in the sinonasal area is generally benign. We report the case of a young woman with a sinonasal mass histologically proven to be haemangiopericytoma. The patient underwent surgical treatment by means of mid-facial degloving after embolisation of the maxillary artery. After a careful 3-year follow-up, the patient is disease free and healthy.

Haemangiopericytoma: histological spectrum, immunohistochemical characterization and prognosis.

Canine haemangiopericytoma (CHP) is a vascular neoplasm thought to be derived from pericytes. The histological pattern and immunohistochemical profile were studied in 31 CHPs. Twenty-three subjects were followed for 2 years to evaluate the correlation among tumour location, histotype, immunostaining and outcome of the disease. Of the 31 CHPs examined, 20 exhibited a perivascular whorled pattern, 8 were storiform and 3 were epithelioid. All tumours were positive for vimentin and negative for cytokeratin, factor VIII-related antigen, glial fibrillary acidic protein and S-100 protein. Seventeen CHPs were positive for actin and nine co-expressed desmin. Six CHPs were also positive for CD34 antigen. The panel of immunohistochemical markers used confirmed the vascular lineage of CHP and aided in the exclusion of other mesenchymal tumours. Of the 23 dogs submitted to follow-up, 6 had recurrence or metastases of the primary tumour. The epithelioid pattern or a noncutaneous location were associated with a poorer prognosis.

Intracranial hemangiopericytomas. Histological and immunohistochemical study.

The authors report on 8 cases of intracranial supratentorial tumors which clinically corresponded to meningeal neoplasms. Only one patient revealed the recurrence. The age of patients was 39-74, prevailed women (5). Histological features of tumors, except some variations in two cases agreed with common morphologic pattern of hemangiopericytomas. Immunohistochemical study with following antibodies was performed: vimentin, epithelial membrane antigen, cytokeratin, S-100 protein, fibronectin, desmin, collagen IV, factor RAg, and glial fibrillary acidic protein. Two atypical cases which presented scarce pseudocalcifications and tendency to concentric cellular structures did not differ from other hemangiopericytomas by their intrinsic immunohistochemical properties such as negative reaction to epithelial membrane antigen and cytokeratin. Atypical positive immunostaining with S-100 protein and with glial fibrillary acidic protein was found solely in the group or perivascular cells in one of those atypical cases reflecting probably local astrocytes embedded in tumor tissue. Immunohistochemical investigations did not present univocal data to explain controversial origin of hemangiopericytomas either from meningeal cup cells or from vascular pericytes.

Immunohistochemical characterization of hemangiopericytomas and other spindle cell tumors in the dog.

The immunohistochemical expression of muscle actin has been studied in 45 canine hemangiopericytomas (CHP) using a monoclonal antibody (HHF35) and formalin-fixed, paraffin-embedded specimens. The distribution of vimentin, desmin, cytokeratins, lysozyme, factor VIII-related antigen, S-100 protein, and glial fibrillary acidic protein was studied both in CHP and in some canine soft-tissue neoplasms (seven fibrosarcomas, seven benign schwannomas, seven benign fibrous histiocytomas, and six leiomyosarcomas) used as controls for differential diagnosis. All CHP and control tumors expressed vimentin. Twenty-three CHP expressed muscle actin, whereas all control tumors analyzed were muscle actin-negative, with the exception of leiomyosarcomas. Among muscle actin- and vimentin-positive CHP, one case could be reclassified as leiomyosarcoma because it was desmin-positive, two cases expressed lysozyme, and nine cases expressed S-100 protein. Among muscle actin-negative and vimentin-positive CHP, seven expressed S-100 protein. In addition, S-100 protein was detected in five schwannomas. All CHP and control tumors analyzed were negative for cytokeratins, factor VIII-related antigen, and glial fibrillary acidic protein. Our results support the hypothesis of a pericytic origin of CHP, and suggest that muscle actin, desmin, vimentin, and lysozyme could be useful for the differential diagnosis of canine spindle cell tumors, but not all these neoplasms can be identified with these tumor tissue markers.

Primary sarcomas of the lung: a clinicopathological and immunohistochemical study of 14 cases.

The clinicopathological features and immunohistochemical findings in 14 primary sarcomas of the lung collected over a 30-year-period are presented. This represents one sarcoma per 550 bronchogenic carcinomas undergoing resection in this centre. The study group comprised six leiomyosarcomas, five malignant peripheral nerve sheath tumours, two haemangiopericytomas and one epithelioid haemangioendothelioma. The majority of cases occurred in men (nine males: five females), with mean age at presentation of 54 years for men and 47 years for women. All leiomyosarcomas were seen in men, whereas malignant peripheral nerve sheath tumours showed no particular sex preponderance. Leiomyosarcomas were larger tumours than malignant peripheral nerve sheath tumours, mean tumour diameter 15 cm (range 10-25 cm) compared to 9.5 cm (7-15 cm), respectively. All leiomyosarcomas were situated intraparenchymally whereas two of the five malignant peripheral nerve sheath tumours were endobronchial in site. Extrathoracic metastates were seen at death in two of the six leiomyosarcomas but not in any of the malignant peripheral nerve sheath tumours. Overall survival was 28 months although for the leiomyosarcoma/malignant peripheral nerve sheath tumour group alone survival was 8 months. Tumour grading appeared to be a more useful prognostic factor than tumour site (endobronchial/parenchymal) or tumour size. Haemangiopericytoma and epithelioid haemangioendothelioma were associated with a more favourable prognosis.

Ki-67 and biological behaviour in meningeal haemangiopericytomas.

The biological behaviour of meningeal haemangiopericytomas was retrospectively studied using immunohistochemical staining with MIB1, a monoclonal antibody against the Ki-67 antigen, a nuclear protein related to cell proliferation. Paraffin-embedded material from 62 tumours from 40 patients were investigated. The proliferating compartment of the tumours was estimated by evaluating the MIB1 staining index, i.e. the percentage of MIB1 positive nuclei in at least 1000 counted tumour cells in representative areas. The staining index ranged from 1.24% to 39.01%. Statistical analysis revealed no significant correlation between the staining index and recurrence-free survival (chi 2 = 0.3922, P = 0.5311). Long-term observation (> 100 months), however, revealed a tendency to longer survival in the group with a staining index less than 5%. According to our results, the MIB1 staining index does not contribute to the accuracy of predicting the clinical outcome of meningeal haemangiopericytomas.

Intermediate filament reactivity in hyperplastic and neoplastic lesions from medaka (Oryzias latipes).

To determine if hyperplastic and neoplastic lesions from medaka showed similar immunoreactivity to intermediate filament antibodies as the tissues of origin, two week old medaka were exposed to 10 or 20 mg/L of methylazoxymethanol acetate for two hours and transferred to clean water for up to six months. Using a streptavidin peroxidase method, paraffin embedded Bouins fixed neoplasms were incubated with cytokeratin, vimentin, or neurofilament antibodies. Like their nonneoplastic cellular counterparts, hepatocellular carcinoma, pancreatic acinar carcinoma and mesenchymal neoplasms including hemangioma and hemangiopericytoma reacted negatively to cytokeratin antibodies. Cholangiocarcinoma, mesothelioma, and proliferative lesions containing biliary epithelial cells reacted positively to cytokeratin antibodies. All neoplasms and proliferative lesions were negative with vimentin and neurofilament antibodies. These data indicate that while some epithelial neoplasms showed cytokeratin reactivity similar to the parent tissues, additional markers are needed to identify mesenchymal tissues and neoplasms.

Haemangiopericytomas: the prognostic value of immunohistochemical staining with a monoclonal antibody to proliferating cell nuclear antigen (PCNA).

Forty-two cases of haemangiopericytoma were studied retrospectively using immunohistochemical staining with PC10, a monoclonal antibody to PCNA. The percentage of tumour cells with positive staining for PCNA was found to correlate well with histological grading. Clinical follow-up data were available in 25 adults and showed no known deaths in 11 cases with a low proportion (less than 14%) of positive cells. Out of 14 cases with a high number (greater than or equal to 14%) of positive cells, seven patients are known to have died, two had metastases, and in a further two there have been multiple recurrences of tumour. DNA flow cytometry was performed on 26 cases but this showed no correlation with PC10 staining or clinical outcome. Staining with PC10 may be of particular value in the identification of patients at greatest risk of rapid tumour metastasis and early death.

Malignant haemangiopericytomas and haemangioendotheliosarcomas: an immunohistochemical study.

Formalin-fixed, paraffin-embedded material from 15 haemangioendotheliosarcomas and eight malignant haemangiopericytomas was stained with an immunohistochemical technique for the presence of factor VIII-related antigen (F VIII-RAg), actin, laminin and for reactivity with the lectin Ulex europaeus I (UEA-I). Haemangioendotheliosarcomas stained with both F VIII-RAg and UEA-1; however, UEA-I was found to be the more sensitive of the two, reacting also with the poorly differentiated tumours. Haemangiopericytomas reacted negatively with UEA-I; surprisingly, some of these tumours exhibited a weak positivity in staining for F VIII-RAg, possibly supporting the theory about intermediate forms between haemangioendotheliosarcomas and haemangiopericytomas. Laminin was found in most of the haemangioendotheliosarcomas and was useful in illustrating their vascular growth pattern. Haemangiopericytomas also reacted positively for laminin, but the intensity of staining was less pronounced. Positive staining for actin was demonstrated in both tumour types.

Congenital hemangiopericytomas of skin.

A case of multiple congenital hemangiopericytomas of skin treated by surgical excision is presented. No recurrence of the lesions has occurred after a period of 2 years.

[T- and B-cell functional activity in the immune response in viral carcinogenesis]. / Issledovanie funktsional'noi aktivnosti T- i B-kletok v immunnom otvete pri virusnom kantserogeneze.

The functional activity of the spleen cells, their ability to produce antibody-forming cells on the model of the adoptive transfer, activity of T-helper-cells and B-precursor-cells of antibody producers in the tumour growth induced by monkey SA7 (C8) adenovirus were studied. The inoculation of the tumourigenic virus to the newborn mice CBA, inhibit antibody formation in the system of adoptive transfer already in the latent period with a sharp inhibition at the terminal stages of carcinogenesis. The helper activity is suppressed earlier than the activity of B-precursors of antibody producers. The obtained data indicate a considerable immunodepressive action of monkey adenovirus SA7 (C8).

[Coombs-positive reactions in mice during transplantation of syngeneic tumors]. / Kumbs-polozhitel'nye reaktsii u myshei pri transplantatsii singennykh opukholei.

The effect of the growth of syngeneic transplantable tumors on Coombs' positive test in mice was studied. The modification of the hemagglutination test permitting one to minimize the amount of reagents used is described. Tumor transplantation induced Coombs' positive reactions in most recipients. The phenomenon could be observed in 4 murine strains and 6 tumor systems. Sometimes autoimmune reactions occurred before the emergence of palpable tumors. It is concluded that despite the influence of nonspecific factors, the principal cause of autoimmune reactivity is tumor growth. It seems that the appearance of alien "normal" histocompatibility antigens is a characteristic feature of all the tumors; besides, the host response pattern to these antigen is cross-reactive, including autoimmune component. Coombs' positive test may be one of numerous manifestations of such an autoimmune process.