Fine-needle aspiration in myxofibrosarcoma: experience of Institut Curie.

Myxofibrosarcoma (MFS) is a well-established nosologic entity different from the myxoid variant of malignant fibrous histiocytoma. In an attempt to better define the representative cytologic criteria of MFS, we undertook a review and a reanalysis of a series of 14 cytology samples in 12 patients whose tumors were diagnosed as MFS.Using FNA technique and reviewing the original diagnoses, 11 cases were diagnosed as malignant and three as benign tumors. The cytologic diagnosis of MFS was accurate in seven cases (2 primary tumors, 4 recurrences, and 1 metastasis). Four cases were classified malignant myxoid sarcoma (1 primary and 3 recurrences), whereas three cases (2 primary and 1 recurrence) were false-negative.The smears were cell-rich in 12 cases and cell-poor in two cases. They were constantly composed of isolated and regular small spindle-shaped and stellated cells with elongated nuclei containing small inconspicuous nucleoli. Cytoplasm was pale with elongated processes. Clusters of wavy spindle-shaped cells, round cells without specific pattern, moderate cytonuclear atypia, and abundant myxoid background as well as curvilinear vascular structures were always seen. In the vast majority of cases, the cytologic distinction of MFS from other low-grade myxoid lesions is difficult. Entities such as myxoid MFH, myxoid liposarcoma (MLP), myxoid DFSP, and myxoma should be considered in the differential diagnosis. The cytological misdiagnosis is of limited clinical consequence because FNA findings suggestive of a myxoid tumor will be indicative for a surgical removal followed by the histopathological analysis.

Cyto-histological correlations in primary, recurrent and metastatic rhabdomyosarcoma: the institut Curie's experience.

To determine diagnostic cytomorphologic features of rhabdomyosarcoma (RMS) on fine-needle aspiration (FNA) material, the cytologic material and corresponding histologic slides of 180 tumors obtained from 109 patients were reviewed. Fifty eight (32.2%) tumors were primary, 34 (18.9%) recurrent, and 88 (48.9%) metastatic. A review of original cytology reports revealed that 176 of 180 (97.8%) tumors were either diagnosed accurately or as round cell sarcoma, while 3 (1.7%) were reported as suspicious. In one case (0.5%), the material was unsatisfactory. No false negative samples were seen. When FNA morphology was correlated with different histological subtypes, the alveolar subtype RMSs were more cellular than the nonalveolar ones (91.4% vs. 64.9%). Similarly, alveolar subtype RMSs compared with nonalveolar ones exhibited more rhabdomyoblastic cells (77.1% vs. 52.7%), alveolar structures (67.6% vs. 10.8%), giant, multinucleated cells (22.9% vs. 6.7%), mitotic figures (57.1% vs. 18.9%), and cyto-nuclear atypia (77.1% vs. 43.2%). Inversely, spindle-shaped cells were more frequently seen in nonalveolar versus alveolar RMSs (37.8% vs. 20.9%).

Cyto-histological correlations in primary, recurrent, and metastatic bone and soft tissue osteosarcoma. Institut Curie's experience.

To determine diagnostic cytomorphologic features of osteosarcoma on fine-needle aspiration materials, we reviewed the cytologic material and corresponding histologic slides of 126 tumors in 107 patients. Fifty-five (43.6%) tumors were primary, 31 (24.6%) were recurrent, and 40 (31.8%) were metastatic. Review of original cytology reports revealed that 120 (95.3%) tumors were diagnosed as malignant. Six (4.7%) cases were reported as suspicious, false-negative, or unsatisfactory samples. Our findings showed that osteoblastic roundish cells, spindle-shaped cells, reactive giant cells, and osteoid were the most consistent features representative of osteosarcoma. Periosteal reactions, fractures with callous formation, giant cells of osteoclastic type in various conditions, chondrosarcoma with enchondral ossification are entities to consider in the differential diagnosis.

Cytohistologic correlations in schwannomas (neurilemmomas), including "ancient," cellular, and epithelioid variants.

Schwannoma accounts for one of the most common benign mesenchymal neoplasms of soft tissues. Although it is well defined in the cytology literature, particular histologic subtypes such as "ancient," cellular and epithelioid variants could be a source of diagnostic difficulties. We have reviewed cytology aspirates and corresponding histologic sections from 34 schwannomas diagnosed at Institut Curie. Histologically, 24 cases were classic, 5 were "ancient," 4 were cellular, and 1 was epithelioid schwannomas. No example of melanotic schwannoma was recorded. Original cytologic diagnosis was schwannoma in 13 (38.2%) cases, benign soft tissue tumor in 11 (32.4%), pleomorphic adenoma in 2 (6%) cases, angioma in 1 (2.9%) case, nodular fasciitis in 1 (2.9%) case, suspicious in 3 (8.8%) cases, and not satisfactory in 3 (8.8%) cases. There were no major differences between classical, "ancient," cellular, and epithelioid variants on cytology smears. Myxoid stroma, mast cells, and intranuclear inclusions were limited to classical subtype. Similarly, cyto-nuclear atypia was more frequent in classical subtype than in other subtypes. Schwannoma should be differentiated from well-differentiated malignant peripheral nerve sheath tumor, neurofibroma, and pleomorphic adenoma, in the last instance particularly for head and neck lesions.

Fine-needle aspiration of primary and recurrent benign fibrous histiocytoma: classic, aneurysmal, and myxoid variants.

There is a limited number of correlative cytopathological studies of fibrous histiocytoma (FHC). To better define cytopathological criteria of diagnosis, we have reviewed fine-needle aspirates (FNA) from 36 FHCs (32 classical, 1 myxoid, and 3 aneurysmal variants on corresponding histological sections). Original cytological diagnoses were benign in 33 (91.7%) cases (22 accurate) and false positive in 3 (8.3%) cases. All smears were surprisingly homogenous and composed of histiocytic cells with finely vacuolated cytoplasm in 27 (75%) cases, small regular spindle cells in 25 (69%) cases, and giant cells in 17 (47%) cases. Histiocytic cells were attached to vascular structures in 9 (25%) cases. Slight cytonuclear atypia was seen in five (14%) cases. Three (8.3%) cases showed numerous siderophages. In two (5.6%) cases, there were abundant inflammatory backgrounds and in one (3%) case there was a scant myxoid background. Storiform patterns, round cells, prominent atypia, necroses, or mitotic figures were not seen. FHC should be differentiated from other benign, low- and intermediate-grade spindle-cell neoplasms such as low-grade fibrosarcoma, dermatofibrosarcoma protuberans, nodular fasciitis, spindle-cell malignant melanoma, and monophasic synovial sarcoma. Some cases may be misinterpreted as malignant, especially in cases of recurrence or in patients with a cancer history.

Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.

High concentrations of oxygen can induce pulmonary toxicity and cause injury to alveolar epithelial and endothelial cells. The present study was performed to determine whether the potent epithelial and endothelial fibroblast growth factor 1 (FGF-1) protected against hyperoxia-induced lung injury. Recombinant adenovirus carrying the gene encoding human secreted FGF-1 (Ad. FGF1) increased the proliferation of lung epithelial cells in vitro. Ad.FGF1 or control vector with an empty expression cassette (Ad.V152) was administered intratracheally to Wistar rats. With Ad.FGF1 (10(9), 5 x 10(9), 10(10), or 5 x 10(10) viral particles [VP]), FGF-1 protein was found in bronchoalveolar lavage fluid 4 days postinfection at levels proportional to the viral dose and was detected in plasma after doses of 10(10) VP or more were administered. Histological examination of the lungs showed intense proliferation and apoptosis of alveolar and bronchial epithelial cells, with few inflammatory cells. The alveolar architecture returned to normal within 17 days. Rats pretreated with Ad.FGF1 (10(9) or 5 x 10(9) VP) 2 days before exposure to hyperoxia (95% O2) survived, whereas rats pretreated with Ad.V152 died within 3 days. In conclusion, adenovirus-mediated FGF-1 overexpression in the lungs causes epithelial cell proliferation and has beneficial effects in hyperoxic lung injury.

Fine-needle sampling in malignant phyllodes tumors: clinicopathologic study of 22 cases seen at the Institut Curie.

The preoperative cytological diagnosis of malignant phyllodes tumor (MPT) is challenging due to the heterogeneity of its clinical, radiological, and morphological presentation. To better define the cytopathological characteristics of MPT, we reviewed 22 examples seen at the Institut Curie. The original cytologic diagnosis was benign breast tumor in four cases (18.2%), suspicious in seven cases (31.8%) (low-grade phyllodes tumor in six cases needing histological evaluation, suspicious of sarcoma in one case), and malignant in 11 cases (50%). Smears were composed of different proportions of clusters of epithelial cells (68.2%), phyllodes fragments (31.8%), spindle cells within stromal tissue (31.8%), isolated spindle-shaped or round cells (45.5%), and bipolar naked nuclei (22.7%). Giant cells and mitotic figures were also occasionally seen. The cytological findings on smears were correlated with histopathological observations. One of the difficulties to reach an accurate cytological diagnosis for MPT is the frequent overwhelming of clearly malignant sarcomatous cell by the presence of largely predominant clusters of epithelial cell.

Fine-needle aspiration in liposarcoma: cytohistologic correlative study including well-differentiated, myxoid, and pleomorphic variants.

We have reviewed cytopathology and the corresponding histopathology material of 86 liposarcomas (55 patients) seen at Institut Curie. The liposarcomas (LS) were well differentiated in 14 cases (9 pure, 2 dedifferentiated, 3 sclerosing), 64 myxoid, and 8 pleomorphic. Twenty-four tumors were primary, 34 recurrent, and 28 secondary. Smears in LS were composed in different proportions of round, spindle cells, lipoblasts, and myxoid and vascular arborizing structures. Pure well-differentiated LS were frequently composed of lipoblasts, and round or spindle cells were occasionally seen. Dedifferentiated and sclerosing liposarcomas were composed of spindle or round cells, but lipoblasts were also occasionally present. Myxoid or vascular arborizing structures were absent. Myxoid LS (including round and spindle cell LS) frequently showed a myxoid background and less frequently vascular arborizing structures. Tumor cells were round or spindle. Lipoblasts were also seen. Pleomorphic LS were composed of an admixture of all cellular and stromal elements. Well-differentiated LS should be distinguished from hibernoma and spindle cell lipoma, and myxoid LS from myxoma, myxoid chondrosarcoma, chordoma, myxoid leiomyosarcoma, and myxoid malignant fibrous histiocytoma. The demonstration of the specific translocation t(12;16)(q13;p11) of myxoid LS is very helpful to establish the diagnosis. Pleomorphic LS should be differentiated from other high-grade sarcomas, whenever possible.

Fine-needle aspiration of primary and recurrent dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans (DFSP) is a nodular cutaneous mesenchymal tumor of intermediate malignancy. Studies on fine-needle aspiration of DFSP are extremely rare; to our knowledge, only 33 cases have been reported. We have reviewed 14 examples of DFSP in 13 patients. Ten primary tumors were aspirated before surgical biopsy and four recurrent lesions (all from superficial lesions) were also investigated by fine-needle aspiration. All smears were surprisingly homogeneous and composed of isolated spindle cells in all cases (one unsatisfactory smear is excluded). Tissue fragments with a stroriform pattern were seen in 11 cases, fibrillary stromal fragments in 10 cases, naked nuclei in 8 cases, slight to moderate cytonuclear atypia in 5 cases. Mitotic figures, myxoid background, mast cells, and dispersed adipocytes were rare. Giant cells, necrosis, or marked cytonuclear atypia were not seen. DFSP shares morphological characteristics of some low-grade spindle-cell neoplasms. It should be differentiated from other benign low- and intermediate-grade spindle neoplasm such as low-grade fibrosarcoma, fibromyxosarcoma, low-grade malignant peripheral nerve sheath tumor, benign peripheral nerve sheath tumor, nodular fasciitis, and fibrous histiocytoma.

Comparative fine-needle aspiration and pathologic study of malignant fibrous histiocytoma: cytodiagnostic features of 95 tumors in 71 patients.

To determine diagnostic cytomorphologic features of malignant fibrous histiocytoma (MFH) on fine-needle aspiration (FNA) materials, we reviewed the cytologic material and corresponding histologic slides of 95 tumors in 71 patients. Forty-four (46%) tumors were primary, 38 (40%) were recurrent, and 13 (14%) were metastatic. Histological variants of MFH were as follows: 52 (54.7%, 43 patients) were of the storiform/pleomorphic, seven (7.4%, five patients) were giant cells, four (4.2%, four patients) were inflammatory, and 31 (33.7%, 19 patients) were myxoid type. Review of original cytology reports showed that only 23 (24.2%) tumors were diagnosed as MFH and 68 (71.6%) as other types of malignancies. Four (4.2%) cases were reported as unsatisfactory/suspicious. Our findings showed that spindle-shaped, round, giant cells, osteoclastic-like giant, and inflammatory cells were the most consistent features that allow identification of the storiform/pleomorphic, giant cell, and inflammatory variants of MFH. The myxoid tumors had marked myxoid background matrix with spindle-shaped cells and, less frequently, round and giant cells. Pleomorphic leiomyosarcoma and dedifferentiated liposarcoma should be considered in the differential diagnosis of stroriphorm/pleomorphic, giant cells, and inflammatory variants of MFH. However, myxoid MFH may resemble their leiomyosarcoma and liposarcoma counterparts.

Cytohistologic correlations in angiosarcoma including classic and epithelioid variants: Institut Curie's experience.

To characterize the cytological features of angiosarcomas, we reviewed the fine-needle aspiration material and corresponding histologic sections of 29 tumors in 23 patients. Histologically, 24 tumors were of the classic type, and 5 were epithelioid angiosarcomas. The original corresponding cytologic diagnoses were as follows: angiosarcoma, 17 cases; sarcoma not otherwise specified, 8 cases; and rhabdomyosarcoma, 1 case. Three samples were cell-poor and were considered suspicious of malignancy. The review of cytology samples showed that smears were cell-rich in 17 tumors and cell-poor in 12 tumors. A hemorrhagic background was present in 9 cases. Tumor cells were polymorphous, including spindle-shaped, round to oval, and polygonal epithelioid cells and giant cells in different proportions. Erythrophagocytosis was seen in 12 tumors. Smears of classic angiosarcomas were polymorphous and lacking specific characteristics, whereas smears of epithelioid tumors were morphologically similar and composed of round to oval and polygonal, epithelial cells frequently arranged in clusters, and showing erythrophagocytosis. The wide spectrum of cellular components of angiosarcomas accounts for the difficulty in establishing accurate tumor typing, particularly with cell-poor samples and low-grade classic angiosarcoma. Entities to consider in the differential diagnosis are carcinoma, epithelioid sarcoma, pleomorphic rhabdomyosarcoma, and malignant melanoma.

Fine-needle aspiration of leiomyosarcoma: a correlative cytohistopathological study of 96 tumors in 68 patients.

To better define the cytological features of various leiomyosarcoma (LMS) variants, we reviewed the fine-needle aspiration material and the corresponding histologic sections of 96 tumors in 68 patients. Histological variants of LMS were as follows: 80 (83.3%) were of the classical/usual, seven (7.3%) were epithelioid, and nine (9.4%) were myxoid. Review of original cytology reports showed that 23 (24%) tumors were diagnosed as LMS and 69 (71.8%) as other types of malignancies. Two (2.1%) cases were reported as suspicious and two (2.1%) were unsatisfactory. The classical variants of LMS were characterized cytologically by various proportions of spindle-shaped, cohesive, small- or large-sized cells arranged in parallel alignment. Large spindle, round, binucleated, giant cells with intracytoplasmic granulations were frequently seen. Blunt-ended nuclei, intranuclear inclusions and mitotic figures were occasionally seen, as well as stromal fragments. The epithelioid tumors were composed of an admixture of small and large, spindle-shaped and round cells, also arranged in parallel alignment. Tumor cells with granular cytoplasm, blunt-ended nuclei, intranuclear inclusions, mitotic figures, fibrous or myxoid stroma were not observed. The myxoid tumors disclosed large amounts of background myxoid matrix containing large spindle-shaped and giant cells. Entities such as leiomyoma, malignant peripheral nerve sheath tumor, monophasic synovial sarcoma, and malignant fibrous histiocytoma should be considered in the differential diagnosis of LMS of the classical type. Epithelioid leiomyoma may share similar cytological features with epithelioid LMS. The cytological features of the myxoid variant of LMS can be easily confused with other types of benign and malignant mesenchymal tumors depicting degenerative myxoid changes and/or a myxoid matrix component.

Role of VEGF-B in the lung during development of chronic hypoxic pulmonary hypertension.

Angiogenic factors exert protective effects on the lung. To investigate the effect of VEGF-B, a factor coexpressed in the lung with VEGF-A, we assessed chronic hypoxic pulmonary hypertension in VEGF-B knockout mice (VEGF-B-/-) and in rats with lung overexpression of VEGF-B induced by adenovirus transfer. No significant difference in pulmonary hemodynamics, right ventricular hypertrophy, distal vessel muscularization, or vascular density was found between VEGF-B-/- and control mice after 3 wk of hypoxia. When overexpressed, VEGF-B(167) or VEGF-B(186) had protective effects similar to those of human VEGF-A(165). Lung endothelial nitric oxide synthase (eNOS) expression was increased by 5 days of hypoxia or VEGF-A adenovirus vector (Ad.VEGF-A) overexpression, whereas VEGF-B(167) or VEGF-B(186) had no effect. With hypoxia or normoxia, the wet-to-dry lung weight ratio was increased 5 days after Ad.VEGF-A administration compared with control (Ad.nul), Ad.VEGF-B(167), or Ad.VEGF-B(186). Endogenous VEGF-B does not counteract the development of hypoxic pulmonary hypertension. However, when overexpressed in the lung, VEGF-B can be as potent as VEGF-A in attenuating pulmonary hypertension, although it has no effect on eNOS expression or vascular permeability.

Cytohistologic correlations in 56 synovial sarcomas in 36 patients: the Institut Curie experience.

Synovial sarcoma (SS) is a high-grade malignant soft tissue tumor that manifests different phenotypic subtypes that may render their cytologic evaluation challenging. Although several cytologic studies of SS have been published, correlative studies of cytologic and corresponding histologic features are limited. To better define the cytological features of various SS forms, we reviewed the cytologic and the corresponding histologic material of 56 tumors from 36 patients. Classical patterns were defined as dispersed or small clusters of cells with bland chromatin, inconspicuous nucleoli, oval to spindle-shaped cytoplasm and branching tumor tissue fragments, vessel stalks, acinar structures in scant mucin background, seen in all 53 (94.7%) cellular cases. Epithelial, squamous, round cells, mast cells, necrosis, comma-like nuclei, marked nuclear atypia, secretory mucin, and rosette-like structures were also occasionally observed. Comparing the histological subtype we noted that epithelial cells and secretory mucin were restricted to biphasic SS, round cells to poorly differentiated SS, and comma-like nuclei to monophasic fibrous SS. We conclude that the classical pattern is highly suggestive of SS of all three monophasic, biphasic, or poorly differentiated subtypes. These characteristics, along with molecular genetic studies, may improve the cytologic diagnosis of SS.

Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST) in 17 patients: the Institut Curie experience.

Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are insufficiently documented in the literature. Cytological and histological specimens in 24 tumors in 17 patients were correlated. The review of the original cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma, and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma. At the review tumors were histologically reclassified as well-differentiated MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well-differentiated MPNST were composed of polymorphous oval to round cells, small spindle-shaped cells with wavy and comma-like naked nuclei, and a fibrillary, delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant and polymorphous cells. The malignant Triton tumor was composed of oval to round rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of polymorphous and round, epithelial-like cells. The cytological diagnosis of MPNST may be difficult, especially in anaplastic tumors. The correlation between the cytological features and the clinical information--origin of the tumor from a nerve trunk, a preexisting neurofibroma, patients with known history of neurofibromatosis 1--could be indicative of an MPNST diagnosis.