Fine-needle aspiration in desmoplastic small round cell tumor: a report of 10 new tumors in 8 patients with clinicopathological and molecular correlations with review of the literature.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare round cell sarcoma entity characterized by a specific t(11;22)(p13;q12) translocation, usually intra-abdominal localization and an aggressive clinical outcome. To date, only 35 DSRCT cases diagnosed by fine-needle aspiration have been described. METHODS: This study reports the cytological diagnosis of DSRCT. Ten tumors from 8 patients were sampled for diagnosis and analyzed to search the characteristic translocation using fluorescence in situ hybridization or reverse transcription polymerase chain reaction methods. RESULTS: Smears were always hypercellular and consisted of nonspecific round cell sarcoma. Nuclei were polymorphic round, kidney-, or heart-shaped. Nuclear molding was usually present. Paranuclear cytoplasmic densities were obvious and noted in 7 cases. Cytonuclear atypia, mitotic figures, numerous crushed nuclei, and apoptosis were frequently seen. Purple-stained stroma was present in 8 cases (ranging from few connective tissue fragments to large hyalinized deposits). Molecular studies based on cytological aspirates were performed in 8 patients. The presence of the fusion gene EWSR1-WT 1 transcript was identified in all, which confirmed the diagnosis of DSRCT. CONCLUSIONS: Smears showing poorly differentiated round cells associated with cytoplasmic densities and connective stoma, in a specific clinical context, young adult age, intra-abdominal localization, suggestive immunocytochemical profile, and a unique cytogenetic abnormality are highly specific and allow an accurate diagnosis of DSRCT.

Fine-needle aspiration as a diagnostic technique in 50 cases of primary Ewing sarcoma/peripheral neuroectodermal tumor. Institut Curie's experience.

Fine-needle aspiration (FNA) followed by a core-needle biopsy during general anesthesia is a method for diagnosing pediatric tumors in our Institute. To complete the diagnosis in the case of round cell sarcomas, cytology material is also used for genomic analyses, that is, karyotyping and molecular biology-derived techniques. Fifty primary Ewing sarcomas/peripheral neuroectodermal tumors (ES/PNET) in 50 patients were sampled. Cytological diagnoses were "malignant" in all cases and accurate (ES/PNET) in 46 (92%). Two (4%) cases were misdiagnosed as neuroblastoma, and two others (4%) as rhabdomyosarcoma and nephroblastoma. No suspicious or false-negative results were rendered. Karyotyping was performed in 20 (40%) cases and was interpretable in 17 cases but not in three cases. Molecular search for ES/PNET fusion transcripts were performed in all cases and were detected in 44 (88%) cases, but not in six (12%) cases. In conclusion, FNA assisted by genomic techniques is powerful methods to accurate diagnose ES/PNET.

Fine-needle aspiration of renal and extrarenal rhabdoid tumors: the experience of the Institut Curie regarding 20 tumors in 13 patients.

BACKGROUND: Rhabdoid tumors (RT) are rare, renal or extrarenal, high-grade malignancies. The cytologic diagnosis may be confirmed if combined with genomic results. In the current study, the authors present the cytologic and ancillary techniques used to diagnose RT in their series of 20 tumors in 13 patients. METHODS: Clinical charts as well as cytologic, histologic, karyotypic, and molecular biology results were reviewed. RESULTS: Twelve fine-needle aspirations (FNAs) were performed for primary diagnosis, 7 were to confirm a metastasis, and 1 was to confirm local recurrence. Primary tumors were in the kidney in 7 cases and 13 were extrarenal. Patient age ranged from 5 months to 26 years. There were 7 females and 6 males. FNAs were cell-rich in 16 cases and cell-poor in 4 cases and revealed a mix of atypical spindle-shaped, round, rhabdoid, or epithelioid cells, singly or in clusters. Mitosis and necrosis occasionally were present. The original cytologic diagnosis was malignant in all cases. There were no unsatisfactory or false-negative samples. In the 12 primary tumors, the preliminary FNA diagnosis was RT in 7 cases (58%), rhabdomyosarcoma in 4 cases (33%), and malignant peripheral nerve sheath tumor in 1 case (8%). Karyotypes were available in 6 cases, 3 of which demonstrated chromosome 22 changes. Fluorescence in situ hybridization revealed loss of probe signals for the SMARCB1 gene locus in 5 cases; DNA sequence analysis performed in 9 cases revealed deletions in codons of the SMARCB1 gene in 7 cases and a mutation in 2 cases. CONCLUSIONS: The primary diagnosis of RT is possible on FNA. In the current study, 12 of 13 cases were diagnosed by FNA with a combination of clinical information, immunocytochemistry, and molecular analysis.

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.

[Low grade fibromyxoid sarcoma: a clinico-pathologic analysis of 7 cases]. / Sarcome fibromyxoïde de bas grade: une étude clinico-pathologique de 7 cas.

OBJECTIVES: Low-grade fibromyxoid sarcoma (LGFMS) is a malignant soft tissue tumor. Despite bland histologic features, a significant number of these tumors metastasize. We describe the clinicopathologic features of 7 new cases of LGFMS including one case of dedifferentiation in a recurrence. MATERIALS AND METHODS: 7 cases obtained from the surgical files of the CHUQ, L'Hôtel-Dieu de Québec or from the consultation files were studied. RESULTS: The patients' age (5 male and 2 female) ranged from 16 to 55 years old. The tumors were located in the thigh (4), the deltoid muscle (2) and in the mesentery (1). They measured from 2.3 to 15 cm (greatest diameter). Histologically, the tumors were characteristically more fibrous than myxoid. Tumors cells were bland, oval to spindle shape, and arranged, at least in part, in a storiform or whorled growth pattern. Cellularity was most prominent in fibrous areas and there were small, sometimes curvilinear vessels in the myxoid areas. Mitotic figures were uncommon. Follow-up of patients ranged from 3 (1/2) months to 22 years. Four patients showed recurrence. One of them demonstrated an area of dedifferentiation into a high grade pleomorphic sarcoma, malignant fibrous histiocytoma (MFH) type. The same patient also had a pulmonary metastasis. CONCLUSION: Differential diagnosis of LGFMS should include intramuscular myxoma, myxoid liposarcoma, myxoid variant of dermatofibrosarcoma protuberans and low grade myxofibrosarcoma. The chimeric FUS/CREB3L2 gene seems to be specific for LGFMS and its expression in the t(7;16)(q33p11) is a useful tool for the differential diagnosis. We report a unique case with areas of high grade sarcoma, MFH type, and areas similar to sclerosing epithelioid fibrosarcoma.

Emergence of disseminated candidiasis caused by Candida krusei during treatment with caspofungin: case report and review of literature.

Current data indicate that caspofungin has in vitro activity against virtually all Candida species. However, we report herein a case of disseminated candidiasis due to Candida krusei which emerged during caspofungin treatment. Lung and brain secondary sites were then successfully treated using a combination of amphotericin B plus flucytosine, amphotericin B lipid complex, and voriconazole, sequentially. Among the total of four well documented cases of refractory invasive candidiasis during caspofungin therapy, the common risk factors appear to involve prior abdominal surgery, persistent foreign body, and anatomical sites where drug concentrations may be sub-optimal for Candida species with increased MICs. Caspofungin failure should be suspected in patients with persistent or emergent signs and symptoms of deep-seated invasive candidiasis.

MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: a comparative analysis of 559 soft tissue neoplasms with genetic data.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) may be difficult to distinguish from benign adipose tumors and from poorly differentiated sarcomas, respectively. Genetically, they are characterized by amplification of MDM2 and CDK4 genes on chromosome 12q13-15. We examined a series of 559 soft tissue tumors (44 ALT-WDLPS, 61 DDLPS, 49 benign adipose tumors, and 405 non-ALT-WDLPS/DDLPS sarcomas) for MDM2 and CDK4 expression using immunohistochemistry. MDM2 and CDK4 immunoexpressions were compared with gene amplification status (as assessed by quantitative PCR and/or comparative genomic hybridization) in 241 neoplasms. Most ALT-WDLPS/DDLPS expressed MDM2 (97%) and CDK4 (92%) as opposed to few benign adipose tumors (MDM2, 5%; CDK4, 2%) and a limited number of non-ALT-WDLSP/DDLPS sarcomas (MDM2, 19%; CDK4, 6%). The sensitivity and specificity of MDM2 and CDK4 immunostainings in identifying ALT-WDLPS/DDLPS among other soft tissue tumors were 97% and 92%, and 83% and 95%, respectively. MDM2 and CDK4 immunostainings were particularly useful to separate ALT-WDLPS from the large group of differentiated adipose tumors, and to distinguish DDLPS from poorly differentiated sarcomas. A strong correlation was observed between MDM2 and CDK4 stainings and gene amplification status. In conclusion, MDM2 and CDK4 immunostainings, which correlate with gene amplification, are helpful adjuncts to differentiate ALT-WDLPS from benign adipose tumors and to separate DDLPS from poorly differentiated sarcomas.

Prognostic significance of lymphovascular invasion in surgically cured rectal carcinoma.

BACKGROUND: Surgery is considered curative in Dukes' B rectal cancer; however, many patients present with early relapse. To identify additional staging information, venous and lymphatic invasion were evaluated as potential prognostic factors. METHODS: Patients with Dukes' B or C rectal disease treated between 1976 and 2001 at a single institution were compared. Patient and treatment characteristics and vascular invasion were documented. The impact of vessel invasion was determined using Cox proportional hazards model. RESULTS: There were 256 Dukes' B patients and 74 Dukes' C cases without vascular invasion. Five-year survival was 76.5% for Dukes' B and 57.1% for Dukes' C patients. Vessel involvement increased the risk of recurrence (hazard ratio [HR] = 3.27, P = .0003) and death (HR = 3.11, P = .002) in B2 patients. The magnitude of these associations were comparable to that of C1 patients for recurrence (HR = 2.81, P = .004) and death (HR = 3.05, P = .005), as well as C2 patients for recurrence (HR = 3.45, P = .0008) and death (HR = 3.87, P = .0005). CONCLUSION: Vascular invasion may be useful in characterizing patients with aggressive Dukes' B disease, who might benefit the most from adjuvant systemic therapy.

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.

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.