PNET-like features of synovial sarcoma of the lung: a pitfall in the cytologic diagnosis of soft-tissue tumors

Fine-needle aspiration (FNA) cytology of soft-tissue tumors is evolving. As more experience is gained, we are becoming aware of potential pitfalls. We describe 2 cases of synovial sarcoma of the lung, primary and metastatic, in patients who had FNA biopsy performed on a lung mass. The cytologic smears showed extremely cellular groups of malignant small round cells, intersected by small blood vessels, with numerous loose single cells, in a background of macrophages and mature lymphocytes. The tumors displayed monomorphic cells forming rosettes and displaying occasional mitoses. A diagnosis of neuroendocrine tumor/primitive neuroepithelial tumor (PNET) was suspected. Furthermore, this suspicion was supported by immunohistochemical stains, which showed positivity for a neuroendocrine marker, Leu 7 (case 1), and for a neural marker, CD 99 (O 13 or HBA 71) (both cases); and negativity for cytokeratins (case 1). The resection specimen of case 1 had mostly tightly packed small round cells, with occasional rosettes, similar to the FNA biopsy, and focal areas composed of spindle cells, organized in a focal fibrosarcoma-like and hemangiopericytoma-like pattern. A balanced translocation between chromosomes X and 18, demonstrated by both karyotyping and fluorescent in situ hybridization (FISH), enabled us to make a diagnosis of synovial sarcoma, which was histologically classified as poorly differentiated. Case 2 was a metastatic biphasic synovial sarcoma of the arm, with a prominent epithelial component. Synovial sarcoma, when composed mainly of small round cells on cytologic smears, is a great mimicker of neuroendocrine/PNET tumors, with light microscopic and immunohistochemical overlap. Awareness of this potential pitfall may aid in preventing a misdiagnosis. Its recognition is of major concern, especially for the poorly differentiated variant, because it is associated with a worse prognosis.     

Fine-needle aspiration cytology of islet cell tumors

Islet cell tumors of the pancreas are neuroendocrine neoplasms whose biologic behavior has been well characterized. Frequently, these tumors produce one or more hormones which may strongly affect the patients' clinical presentation. In this study, we have examined fine-needle aspirates (FNA) from 13 islet cell tumors and have summarized their cytomorphologic appearances. The smears prepared from aspirates of the islet cell tumors displayed loose cellular arrangements and numerous single cells, with most cases demonstrating a predominance of single cells over the loose groups. An important diagnostic feature was the uniform appearance of the neoplastic cells. Nuclei were small to moderate in size, always round to oval in shape, and frequently contained small nucleoli. In 11 cases, the nuclear chromatin pattern was finely granular and evenly distributed while in two cases the chromatin was coarser. Eccentrically located nuclei were commonly found and binucleated cells were seen in one-half of the aspirates. At least a moderate amount of finely granular cytoplasm was always identifiable. Immunocytochemical stains for neuron-specific enolase were positive in all five of our cases in which staining for this marker was attempted and chromogranin was positive in five of six cases. Generally, our cytomorphologic observations were supported by the findings of other investigators as reported in the cytology literature. The cytomorphologic characteristics of islet cell tumors are distinctive, and appropriate ancillary studies can be used to support the FNA diagnosis of this entity. Diagn Cytopathol 1996;15:37–45. © 1996 Wiley-Liss, Inc.     

Cytopathology of follicular dendritic cell tumors

Follicular dendritic cell tumors are rarely described entities, arising from antigen-presenting immune accessory cells, found within B-lymphocyte follicles in nodal and extranodal sites. We report two cases, one associated with Castleman's disease, in whom fine-needle aspiration biopsy was performed followed by surgical biopsy. The diagnosis was confirmed using immunoreactivity with CD21 and CD35 antibodies and by ultrastructural demonstration of interdigitating cell processes with desmosomes. Both the cytologic and histologic findings are presented, and the differential diagnoses are discussed. Awareness of this entity and recognition of the pathologic features may lead to a presumptive diagnosis which must be confirmed using immunohistochemistry and/or electron microscopy. Diagn. Cytopathol. 17:138–142, 1997. © 1997 Wiley-Liss, Inc.     

Morphological and immunocytochemical diagnosis of thyroiditis: Comparison between conventional and liquid-based cytology

The efficacy of thyroid (FNAB) processed by liquid-based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto-histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied. 150 cases of HT processed by conventional smear (CS) in 1996-98 and 670 with LBC in 2005-2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow-up (including a second FNA or surgery) was done in 92 cases, in the second period in 116. In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005-2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME-1 and Galectin-3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC. LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions     

Thymic epithelial cells as a diagnostic pitfall in the fine-needle aspiration diagnosis of primary mediastinal lymphoma

The cytologic diagnosis of primary mediastinal lesions is challenging due to the large number of lesions which may arise (i.e., lymphoma, thymoma, germ cell tumor), often with overlapping cytomorphologic features. We present an instructive case of primary mediastinal non-Hodgkin's large-cell lymphoma with sclerosis, entrapping thymic epithelium. Preoperative fine-needle aspiration yielded predominantly epithelial fragments and few lymphoid cells, leading to the cytologic misdiagnosis of thymoma. The entity of primary mediastinal large-cell lymphoma (LCL) is discussed and correlated with the cytologic features seen. In addition, histologic sections from 15 additional cases of primary mediastinal LCL were evaluated to determine the frequency with which significant numbers of epithelial fragments may be observed. Diagn. Cytopathol. 16:460–465, 1997. © 1997 Wiley-Liss, Inc.     

Psammomatous melanotic Schwannoma localized in the mediastinum: diagnosis by fine-needle aspiration cytology

The cytological characteristics are presented in a case of psammomatous melanotic schwannoma localized in the mediastinum, diagnosed by fine-needle aspiration cytology (FNAC), with later histological confirmation. This lesion affected a 38-year-old male, with a tumor measuring 5 cm in diameter located in the posterior mediastinum in contact with the spinal cord, with erosion of the adjacent vertebra (T5), that caused constant pain localized in the right scapular region with an evolution of several weeks. The cytological characteristics of psammomatous melanotic schwannoma are discussed, along with the histological and immunohistochemical features of this infrequent neural tumor, which aid in establishing a differential diagnosis. The importance of a correct histological diagnosis of this tumor is of particular clinical relevance after having been identified as one of the possible components of Carney's complex. This possibility demands a meticulous patient exploration in search of any other components that make up this complex, given the aggressive character of some of them. These lesions could, if not detected early enough, produce fatal consequences for the patient, fundamentally in those patients with cardiac myxomas. In this case, following an exhaustive clinical examination there was no pathology associated with this complex. It is therefore considered to be an isolated psammomatous melanotic schwannoma, and not a part of Carney's complex. Diagn. Cytopathol. 1998;19:298–302. © 1998 Wiley-Liss, Inc.     

细针吸取细胞学检查对乳腺良性病变的鉴别诊断

目的 :探讨鉴别纤维囊性乳腺病和乳腺纤维腺瘤细针吸取细胞学 (FNAC)的主要细胞形态学指标。方法 :运用Logistic多重回归模型的统计分析方法 ,对 2 2 4例有活检证实的乳腺FNAC的良性病变 (4 8例纤维囊性乳腺病和 176例纤维腺瘤 )的5 4个细胞学指标进行分析 ,指标的评价采用 0～ 3 的分级评价方式。结果 :研究发现 ,最有价值的鉴别指标是细胞量 (P =0 0 0 1) ,次要指标是背景的游离肌上皮细胞量 (P <0 0 5 )。组合细胞量 (2～ 3 )和背景的游离肌上皮细胞量 (2～ 3 )作为联合指标进行评价 ,可将纤维腺瘤的阳性预测价值提高至 93 5 %。结果发现 ,在乳腺FNAC检查中 ,分叶结节状的间质在纤维囊性乳腺病和乳腺纤维腺瘤中的发生率存在明显的差异性。结论 :在乳腺细针吸取细胞学的良性病变中 ,细胞量和背景的游离肌上皮细胞量是鉴别纤维囊性乳腺病和纤维腺瘤的最有价值的细胞形态学指标。分叶结节状的间质是管内型纤维腺瘤的间质的组织形态在FNAC中的表现 ,是诊断纤维腺瘤的特征性指标 ,对诊断纤维腺瘤有重要的意义     

Fine-needle aspiration biopsy of metastatic Ewing's sarcoma with MIC2 (CD99) immunocytochemistry

The use of fine-needle aspiration biopsy (FNAB) has been infrequently described as a diagnostic modality for Ewing's sarcoma (ES) patient follow-up and management. The purpose of this study is to examine the use and accuracy of FNAB combined with MIC2 immunocytochemistry for evaluating metastases in patients with ES. Records from Saint Louis University Health Sciences Center and Indiana University Medical Centers identified patients with known ES who had undergone FNAB for evaluation of potential metastases. Immunocytochemical analysis for MIC2 (CD99) was performed retrospectively on cell blocks and direct aspirate smears. FNABs from nine patients were procured either percutaneously or under radiologic guidance and in all cases a definitive cytologic diagnosis of metastatic ES was rendered. Aspirates were cellular with many single discohesive small round cells and occasional loosely cohesive clusters. The nuclei were round with a fine chromatin pattern and small nucleoli. The cytoplasm was scanty and the nuclear-cytoplasmic ratio was high. Six of six cases showed strongly positive immunocytochemical labeling for MIC2. Immunocytochemistry with MIC2 in FNAB aspirate smears can provide supportive evidence of ES in patients with known disease. Diagn. Cytopathol. 1998;19:382–384. © 1998 Wiley-Liss, Inc.     

Leydig cell tumor of the testis: A cytohistological,immunohistochemical, and ultrastructural case study

We report a case of Leydig cell tumor of the testis in a young man, in whom preoperative diagnosis was achieved by fine-needle aspiration biopsy cytology. Cytology, histology, and ultrastructural examination showed diagnostic Reinke's crystals, both in nuclei and in cytoplasm. Immunohistochemistry displayed strong vimentin and estrogen positivity. Diagn. Cytopathol. 16:262–266, 1997. © 1997 Wiley-Liss, Inc.     

Nucleolar organizer regions in small cell tumours of childhood

A silver colloid technique for nucleolar organizer regions (AgNORs) was applied to paraffin sections of 50 small cell tumours of childhood. These comprised 20 neuroblastomas, 10 Ewing's sarcoma, and 20 rhabdomyosarcomas, including spindle cell, myxoid, and round cell variants. On the basis of the number of AgNORs, one could differentiate between the three groups. The differences observed were statistically significant (P = 0.01-0.001). The subtypes of rhabdomyosarcoma could not be distinguished from one another on the basis of AgNOR counts. We suggest that this simple histochemical technique may be a useful adjunct to the range of special techniques now available to assist the pathologist in the diagnosis of small round cell tumours.     

From conventional fluid cytology to unusual histological diagnosis: Report of four cases

Malignant small round cell tumors represent a diagnostic challenge for cytologists and pathologists. This case series describes four cases of unusual metastasis of small round cell tumors subtypes into body cavities generating effusions in which fluid cytological examination suggested the neuroendocrine origin of the tumors. Tumor diagnosis (Ewing sarcoma/primitive neuroectodermal tumor and desmoplastic small round cell tumors) were unknown at the cytological evaluation. We can highlight the importance of the accurate analyses of body fluids, both for early diagnosis of metastatic disease, and for the diagnosis of primary tumor when serous effusion is the first manifestation of the neoplasia. Diagn. Cytopathol. 2013;41:348–353. © 2011 Wiley Periodicals, Inc.     

Localization of p53 and proliferating cell nuclear antigen in fine-needle aspirates of benign and primary malignant tumors of the human breast: An immunocytochemical study using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method

p53 and proliferating cell nuclear antigen (PCNA) status was determined in fine-needle aspirates (FNAs) and methacarn-fixed paraffin-embedded tissue sections of six fibroadenomas and 50 primary breast carcinomas using supersensitive monoclonal antibodies and the biotin-streptavidin-amplified method. Nuclear accumulation of p53 was identified in 28% of carcinomas, while a heterogeneous immunostaining for PCNA was seen in all benign and malignant tumors examined. p53 expression in relation to nuclear pleomorphism and lymph-node status showed weak correlation only as to nuclear grade (r=0.28; P < 0.01). No direct or inverse correlation was found to exist between PCNA score and the evaluated prognostic parameters. In conclusion, although the identification of p53 in FNAs of breast tumors may assist in the diagnosis of malignancy, its application in the laboratory practice of cytopathology appears to be limited, since only 28% of primary breast carcinomas accumulate p53. Moreover, PCNA immunocytochemistry can be used as an alternative to traditional methods of evaluating the proliferative rate of tumors in FNAs. Diagn Cytopathol 1996;15:277–281. © 1996 Wiley-Liss, Inc.     

Primary Ewing sarcoma/PNET of the kidney: fine-needle aspiration, histology, and dual color break apart FISH Assay

A 34-year-old previously healthy Hispanic man presented with lower back pain. CT scan revealed an 8-cm space-occupying lesion in the superior pole of the left kidney with numerous small lytic lesions in the skull, vertebrae, ribs, and pelvic bones. CT-guided fine-needle aspiration biopsy revealed a high-grade primitive small round cell tumor with the tumor cells being strongly positive for CD99 and vimentin. The patient subsequently underwent a left nephrectomy. Fluorescence in situ hybridization analysis using a DNA probe for the Ewing Sarcoma breakpoint region 1 (EWSR1) on chromosome 22g12 revealed a rearrangement of the EWSR1 locus. The diagnosis of primary Ewing sarcoma/primitive neuroectodermal tumor of the kidney was established.     

Diagnostic pitfalls in fine needle aspiration biopsy of the spleen

Fine needle aspiration (FNA) of the spleen is rarely performed, due to fear of procedure complications. The objective of this study is to review the cytologic diagnoses of aspiration biopsy of the spleen performed in a cancer center.Archival material (9-year period) was reviewed and correlated with histologic and ancillary test results, when available.Forty-one splenic FNA specimens were identified. There were no reported procedure complications. Nineteen cases were diagnosed as malignant. Of these, 11 were lymphomas. Nineteen cases were diagnosed as benign. There was one false-negative case and four false-positive cases. Primary splenic neoplasms were rare and misinterpreted as malignant.It is important to be familiar with the normal cytology of this uncommonly aspirated organ in order to successfully identify neoplastic and malignant processes. The use of ancillary studies is important in the definitive classification of benign and malignant splenic lesions.     

Diagnostic findings of ultrasound-guided fine-needle aspiration cytology for gastrointestinal stromal tumors: Proposal of a combined cytology with newly defined features and histology diagnosis

Recently, endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has been applied for diagnosis of gastrointestinal submucosal tumors. There have been no definite criteria, however, for the adequate cytological diagnosis of gastrointestinal stromal tumor (GIST) in practice. To facilitate this a novel method is proposed that combines cytology and histology. For 49 cases of submucosal tumor of gastrointestinal tract, EUS-FNA was performed. The aspirated materials were processed for cytology and histology. Both cytological and histological findings were examined on immunocytochemical and immunohistochemical staining of c-kit. Of 49 cases, 40 (81.6%) proved adequate for cytological and/or histological examination. On cytology, cluster types were classified into type A (piled clusters with high cellularity showing a fascicular pattern), type B (thin layered clusters with high cellularity showing a fascicular pattern), and type C (mono-layered clusters or scattered cells). Types A and B were strongly associated with histological diagnosis of GIST. Type C clusters needed confirmation on c-kit positivity and histology. Thus, the combined cytology with newly defined features, and classification and histological diagnostic method for EUS-FNA materials can contribute to improved routine diagnosis for GIST.     

Diagnostic significance of signet ring cells in fine-needle aspirates of the breast

Fine-needle aspiration (FNA) is a reliable and cost-effective procedure in the evaluation and management of breast lesions. One diagnostic dilemma that may sometimes arise is the finding of signet ring cells. The isolated finding of such cells in aspirate smears may be particularly problematic in cases of low cellularity or those with otherwise benign features. Although it is generally held that such cells are almost exclusively associated with carcinoma (particularly the lobular subtype), their significance in FNA smears has never been systematically evaluated. To establish their diagnostic utility, we evaluated aspirate smears from 150 cases of histologically proven benign (77) and malignant (73) breast lesions for the presence of signet ring cells, defined as those containing a prominent intracytoplasmic vacuole with nuclear displacement. Signet ring cells were identified in 71% of malignant cases (75% of ductal carcinomas and 71% of lobular carcinomas), mostly as single cells or within small, loosely cohesive tissue fragments. Such cells were also present in 6% of histologically proven benign lesions, most commonly within large tissue fragments. Many of these cells were proven to be vacuolated myoepithelial cells, based on histologic correlation and immunostaining results using anti-muscle-specific actin. On the basis of these findings, we conclude that (1) the presence of signet ring cells within small loose tissue fragments or as single cells in FNA smears should prompt close clinical follow-up (including repeat FNA and perhaps surgical biopsy), regardless of smear cellularity, (2) the presence of signet ring cells in cases of adenocarcinoma does not predict a particular tumor subtype, and (3) rare benign breast lesions may contain signet ring cells, particularly within large tissue fragments, and do not, in isolation, warrant surgical biopsy to exclude malignancy. Diagn. Cytopathol. 16:117–121, 1997. © 1997 Wiley-Liss, Inc.     

Flow-cytometric algorithm on fine-needle aspirates for the clinical workup of patients with lymphadenopathy

To analyze the value and limitations of flow cytometry (FCM) in the investigation of patients with lymphadenopathy, a retrospective study of 196 patients, referred for fine-needle aspiration (FNA) cytology, was carried out in Canberra, Australian Capital Territory, Australia, between 1992–1997. Complete cytological, flow-cytometric, and outcome (clinical and histological) data were available on all the cases. The FNA appearances were read in conjunction with FCM findings. The following cytological categories were recognized: benign, 78 cases (39.8%); indeterminate, 9 cases (4.6%); and malignant, 109 cases (55.6%). None of the 78 cytologically benign cases had malignant outcome. All 109 cytologically malignant cases had malignant histology, and 8/9 of the cytologically indeterminate FNAs had malignant histology. The cytologically malignant category contained 106 B-cell lymphomas and three T-cell lymphomas. All 65 B-cell lymphomas with K light chain predominance had K/L ratio greater than 3/1, and all 34 B-cell lymphomas with L light chain predominance had an L/K ratio greater than 2/1. Clonality was therefore established for K/L and L/K at 3/1 and 2/1, respectively. When K/L and L/K ratios were below these figures (7 cases), other parameters, including the proportion of CD20 and the dual expression of CD19/CD10 and CD20/CD5, were used to determine the nature of the aspirate. In the B-cell lymphomas without demonstrable light chain restriction, CD20 positivity in excess of 85%, CD19/CD10 positivity of more than 18%, or CD20/CD5 positivity greater than 35% were independently diagnostic of B-cell lymphoma. In the T-cell lymphomas, greater than 90% of the cells were T cells, and aberrant T-cell antigen expression with loss of at least one pan-T-cell antigen was detected. In conclusion, the sensitivity of diagnosis of malignancy, false-negative rate, and predictive value of malignant diagnosis with combined FNA cytology and FCM were 99%, 0%, and 100%, respectively. Diagn. Cytopathol. 1998; 19:274–278. © 1998 Wiley-Liss, Inc.     

Diagnostic accuracy of imprint cytology in the assessment of Hodgkin's disease in Japan

Our objective was to evaluate the usefulness of cytomorphologic assessment in the accuracy of diagnosis of Hodgkin's disease (HD), using imprint cytological preparations over a 18-yr period. Imprint materials from 34 HD cases were reviewed using cytomorphological and immunocytochemical studies. Twenty-six cases (76.5%) were diagnosed to be HD and 6 cases (17.6%) were suspected to be HD, but 2 cases (5.9%) were cytologically diagnosed as reactive lesions, because of an insufficient number of Reed-Sternberg (RS) cells. The 6 suspected cases were definitively diagnosed as HD, using immunocytochemistry. Immunophenotyping of RS cells in 32 cases (excluding the two cases of reactive lesions) showed CD30+ in 31 (96.9%) cases, CD15+ in 22 (68.8%) cases and CD20+ in 12 (37.5%) cases. RS cells were immunophenotypically classified into five groups: A, (CD 30+, 15+, 20-) 15 (46.9%); B, (CD30+, 15-, 20-) 5 (15.6%); C, (CD 30+, 15+, 20+) 6 (18.8%); D, (CD30+, 15-, 20+) 5 (15.6%); and E, (CD30-, 15+, 20+) 1 (3.1%). Cytomorphologic differences in RS cells were identified between group D and other groups (CD15+ and/ or CD20-). The former had a low polymorphic shape (like popcorn), and the latter had a more classical polymorphic shape. Epstein-Barr virus (EBV)-latent membrane protein-1(LMP-1) was identified in 16 (50%) cases. LMP-1 expression was found not only in classic RS cells, but also in smaller variants. These variants did not match the morphologic criteria of RS cells, but expressed the common phenotype (CD30+, CD15+/-) of RS cells, suggesting the same cellular origin as RS cells. This study demonstrated that imprint cytology from lymph node biopsies can be a useful tool for the diagnosis and the evaluation of the cellular biology of HD.     

Dipeptidyl aminopeptidase IV in the cytologic diagnosis of thyroid carcinoma

Recently, the demonstration of DAP IV activity in thyroid cells aspirates has been proposed as an useful tool for the diagnosis of malignancy. We have studied the enzymatic activity of DAP IV, using the modified method of Lodja, in a series of 336 selected aspirates of the thyroid gland with the following cytologic diagnosis: 236 nodular hyperplasias, 60 follicular proliferations, eight Hashimoto's thyroiditis, eight Hürthle-cell proliferations, 20 papillary carcinomas, two anaplastic carcinomas, and two medullary carcinomas. The results were subjectively evaluated on the basis of staining intensity and extension in a minimum of 200 cells. Strong-to-moderate enzymatic activity with an extension of more than 40% of the cells were exclusively seen in follicular-cell derived carcinomas (papillary carcinoma, Hürthle-cell carcinoma, and follicular carcinoma). Medullary carcinoma, anaplastic carcinoma, and benign conditions were negative or weakly stained. Cytohistologic correlation in 88 patients operated on showed the following results: 26 nodular hyperplasia (18 nodular hyperplasia and eight follicular adenomas), 36 follicular proliferation (24 nodular hyperplasia, six, adenomas, three papillary carcinomas, three follicular carcinomas), two Hürthle-cell proliferation (one Hürthle-cell adenoma and one Hürthle-cell carcinoma), 20 papillary carcinomas, two medullary carcinomas, and two anaplastic carcinomas. DAP IV staining was moderate to strong and extensive in all malignant tumors initially diagnosed as follicular or Hürthle-cell proliferations. We conclude that DAP IV activity is present in malignant differentiated thyroid tumors of follicular cells (papillary carcinoma, follicular carcinoma, Hürthle-cell carcinoma), but it is identified neither in medullary carcinoma nor in anaplastic carcinoma. Therefore, its usefulness is restricted to the diagnosis of follicular-cell malignancies. Diagn. Cytopathol. 1998;19:4–8. © 1998 Wiley-Liss, Inc.