In the investigation of superficial lymphadenopathy of unknown cause, fine needle aspiration (FNA) cytology plays an invaluable role. It enables the differentiation of benign lymphadenopathy from lymphoid and non-lymphoid malignancies, obviating the need for open biopsy, and allowing the triage of patients. Cytopathologists should be familiar with the typical FNA patterns of benign lymphadenopathy, and recognize and differentiate among categories. In a minority of cases of benign lymphadenopathy, FNA can render a specific diagnosis. Benign lymphadenopathies are generally categorized into reactive lymphoid hyperplasia (RLH), inflammatory or infectious processes, and benign lymphoproliferative disorders. RLH characteristically presents with a heterogeneous and polymorphous smear composed of normal cellular constituents of lymph nodes, in contrast with the homogeneous or monomorphic smear of most lymphomas. The caveat is that various malignant disorders may also present with polymorphous populations. It is also important to recognize thatbenign lymphoid smears may sometimes contain atypical cells that raise the suspicion of malignancy. Clinical information should always be the integral part of the diagnostic criteria in FNA of lymphadenopathy. If there is any doubt about the benign nature of the smear, it is prudent to suggest biopsy and ancillary studies.

Evaluation of serous effusions can include immunocytochemical stains that differentiate reactive mesothelial cell from adenocarcinoma cell. Among several positive mesothelial cell markers, we used desmin, CK5/6, WT1 and calretinin all known to have high sensitivity and specificity as selective mesothelial cell markers. We studied smears obtained with cytospin from 15 malignant and eight benign effusions. The mesothelial cells were positively stained by desmin, CK5/6, WT1 and calretinin in 60.9%, 29.1%, 26.7% and 56.5%, respectively among 8 benign and 15 malignant effusions; the adenocarcinoma cells were positively stained 6.7%, 13.3%, 1.0% and 0.0%, respectively among 15 malignant effusions. The percentage of positively stained mesothelial cells were somewhat lower for all antibodies compared to the results of previous studies. This was likely due to the differences in preparation methods and fixatives among studies. In conclusion, the use of desmin and calretinin were more valuable than CK5/6 and WT1 for distinguishing between reactive mesothelial cell and adenocarcinoma cells in serous effusion; however, choice of the proper preparation methods and fixatives are also important

The diagnosis of papillary thyroid cancer is generally based on the findings of intranuclear cytoplasmic inclusions and nuclear grooves. Although anisokaryosis and poikilokaryosis, in papillary thyroid cancer, are not distinct when compared to other cancers, cytological examination can provide useful preoperative information. Our study evaluated the diagnostic role of computer-assisted image analysis for the pre-surgical assessment of papillary thyroid carcinoma. Thyroid aspirates from twenty female patients who were histologically confirmed to have both papillary carcinoma and benign nodules were studied. Different populations of 50 benign cells and 50 malignant cells were analyzed. Five morphometric parameters were selected for analysis: nuclear area, perimeter, maximum length, maximum width and intensity standard variation. The values obtained for papillary carcinomas were higher than the surrounding benign nodules as follows: nuclear area 63.5 vs. 36.1 (p=0.000), nuclear perimeter were 29.4 vs. 22.0 (p=0.000), maximum length 9.6 vs. 7.1 (p=0.000), maximum width 8.2 vs. 6.3 (p=0.000), the ratio between maximal length and maximal width 1.16 vs. 1.13 (p=0.000), the standard variation of intensity 14.9 vs. 15.9 (p=0.101) respectively. Therefore, morphometric information can be helpful for the differential cytological diagnosis of papillary thyroid carcinoma.

Distinguishing small cell carcinoma from other lung malignancies is of great clinico-therapeutic significance. Small cell carcinoma is an aggressive tumor with a tendency to metastasize early. Survival time if untreated is low but this tumor is highly responsive to chemotherapy. We have occasionally experienced difficulties in differentiation between adenocarcinoma and small cell carcinoma of the lung in fine needle aspiration cytology (FNAC). The aim of this study was to investigate the possibility of distinguishing small cell carcinoma from adenocarcinoma of the lung in FNAC. We evaluated cytomorphological features of FNAC specimens from 62 small cell carcinomas and 57 adenocarcinomas from the lung that were confirmed by biopsy and/or immunohistochemistry on cell block. Cytomorphological details of the two tumors were compared. Nuclear smearing and nearly absent cytoplasm were the most distinct findings in small cell carcinoma compared to adenocarcinoma (p<0.05). Necrotic background, architecture and chromatin pattern, nuclear molding and nucleoli were significantly different (p<0.05). Nuclear size, nuclear membrane nature and nuclear size variation however were not helpful in distinguishing the two tumors. Combining several features described above, small cell carcinoma can be properly differentiated from adenocarcinoma on FNAC. FNAC is proposed as a diagnostic tool of small cell carcinoma of the lung in the case of inaccessibility to biopsy, and so may allow the proper therapeutic strategies to be determined in such cases

To study the differentiating cytomorphological features of Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) using fine needle aspiration cytology (FNAC), cytomorphological features of 16 patients with HL (n=8) or ALCL (n=8) were analyzed. In the initial cytological diagnosis prior to biopsy, HLs were properly diagnosed in 4 out of 8 cases (4 HL, 2 atypical, 2 benign), whereas all ALCL were diagnosed as malignancies. However, correct diagnosis of non-Hodgkin lymphoma (NHL) was made in only two ALCL patients (2 NHL, 1 HL, 1 sarcoma, 4 malignancy without specific type). Overall, the percentage of large abnormal cells ranged from 30% to 90% in ALCL except for one case, whereas it was less than 5% in all 8 HL. A spectrum of atypical cells was more characteristic of ALCL. In contrast, HL showed an sharp difference between reactive lymphoid cells and neoplastic ones (bimorphic pattern). Moreover, the emergence of kidney-shaped abnormal cells or wreath-like multinucleated cells was helpful in diagnosing ALCL. The combination of thesefeatures would be useful in differentiating HL and ALCL. Nevertheless, these two types of lymphomas cannot be definitely distinguished based on cytomorphological features alone. Therefore, the aim of FNAC would be to suggest a specific diagnosis and indicate the need for a biopsy.

Villoglandular adenocarcinoma of uterine cervix has recently been described, and is characterized by good prognosis and occurrence in young women, except a small number of cases. Morphologically, it exclusively shows villoglandular growth and mild to moderate nuclear atypia, the cytologic diagnoses have been frequently missed due to interpretation error. We report here on the cytologic findings of two cases, and both cases were not diagnosed as adenocarcinoma before punch biopsy. One of these cases showed previously described characteristic features such as high cellularity and large tissue fragments with long villous fronds lined by columnar cell with mild nuclear atypia. The other showed moderate cellularity of somewhat smaller clusters without long villous structures. The clusters showed marked nuclear overlapping and the nuclei showed distinct moderate atypia with hyperchromasia and coarse chromatin pattern. The nucleoli were indistinct. Recognition of these features will be helpful to avoid underdiagnosis as a benign lesion, although diagnosis is still difficult in a portion of the cases.

Merkel cell carcinoma (MCC), a rare primary cutaneous small cell neuroendocrine carcinoma, is a tumor with distinct cytological features. In many cases, immunohistochemical staining (IHC) is required for the differentiation from other small round cell malignancies. Here we describe the cytological findings of Merkel cell carcinoma; these findings contributed to the diagnosis prior to performing IHC. A lower eyelid mass was excised and submitted for frozen section diagnosis. The frozen section diagnosis was consistent with a malignancy, but the more specific diagnosis was limited by the lack of specific histological features. Touch imprint cytology revealed a high cellularity with loosely cohesive small to large sized cells. The tumor cells showed hyperchromatic nuclei with fine chromatin and inconspicuous nucleoli, and thin-rimmed-cytoplasm including the characteristic eosinophilic button-like paranuclear inclusion, previously described as a pathognomonic cytological finding of MCC; this was not found in the H&E frozen section. In conclusion, we suggest that the touch imprint cytology may help in the differential diagnosis of small round cell neoplasms prior to performing IHC especially in frozen section diagnosis.

Due to its nuclear pleomorphism, knowledge regarding the cytological findings of cerebellar hemangioblastoma can lead to misdiagnosis when using squash specimens, which in other circumstances serves as a useful adjunct in the diagnosis of brain tumors on frozen section. We recently experienced the cytological findings of a cellular variant of cerebellar hemangioblastoma in a 51-year-old man. Squash specimens revealed scattered single tumor cells, with pleomorphic nuclei and cytoplasmic vacuoles, on a hemorrhagic background. The cellular clusters were composed of spindle-shaped endothelial cellsin addition to densely clustered stromal cells. Intranuclear inclusions were frequently seen. The nuclear pleomorphism, bubbly cytoplasmic vacuoles and presence of intranuclear inclusions, seen in the squash specimen, may increase the difficulty of frozen section diagnosis of cerebellar hemangioblastoma. Awareness of the cytologicalfindings of hemangioblastoma is needed to avoid the pitfalls in the intraoperative diagnosis of cerebellar hemangioblastomas.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare soft tissue tumor. There have been only a few prior fine-needle aspiration (FNA) cytological reports. Recognition of this tumor is important because of its potential for metastasis despite its indolent nature and its deceptively bland cytologic appearance. A 60-year-old male presented with a slowly growing mass in the left calf detected 10 years ago. The patient underwent surgical excision. FNA cytology was performed directly on the mass. The smears showed low cellularity composed of hypercellular tissue fragments, hypocellular loose aggregates, and stripped nuclei. The cytoplasm was seen as either collagenous material or very thin fibrillary collagen strands. Tumor cells had spindle, ovoid, or irregular nuclei, fine chromatin, and small nucleoli. Focally slight degree of nuclear pleomorphism is noted. There were no mitotic figures. Blood vessels were frequently seen. Immunocytochemically, tumor cells were negative for S-100 protein, desmin, smooth muscle actin, and CD34. The diagnosis of LGFMS is rarely possible by cytology alone; however, LGFMS should be included in the differential diagnosis of spindle-cell tumors consisting of hypercellular and hypocellular components with some capillary-sized vessels arising in the deep soft tissue of the lower extremities, particularly the thigh. The immunocytochemical findings are of help in the differential diagnosis.

Recently, we experienced a case of Angioimmunoblastic T-cell lymphom (AITL) in a 60-year-old man presented with lymphadenopathy, which is first cytological report in Korea. The cytological features showed a heterogeneous population of small to medium-sized lymphocytes, immunoblasts, and plasma cells. Characteristically, there were also a distinct population of follicular dendritic cells admixed with lymphoid cells, forming the so-called dendritic cell-lymphocyte complexes. Histological features showed the classic morphologic features of AITL. Recognition of the characteristic cytological features can suggest the possibility of AITL.