Search

BACKGROUND Appropriate surgical treatment of epithelial ovarian tumors is reliant on intraoperative diagnosis. A retrospective study to compare the diagnostic accuracies of imprint cytology (IC) with frozen section histology (FSH) in these tumors was performed. METHODS About 78 cases of IC-based and FSH-based diagnoses against the final histopathologic diagnoses in terms of both histologic subtype (serous, mucinous, endometrioid, or clear cell tumor) and behavioral type (benign, borderline, or malignant) were compared. The cytomorphologic features of the tumor cells (nuclear atypia, papillary clusters, adenoma cells, and necrosis) in relation to behavioral types were also evaluated. RESULTS While the diagnostic accuracy of IC and FSH were similar with respect to behavioral type (87% and 88%, respectively), the diagnostic accuracy of IC was superior to that of FSH with respect to histologic subtype (83% and 74%, respectively). Among histopathologically confirmed malignant tumors, the diagnostic accuracy of IC (62/64; 97%) was superior to that of FSH (58/64; 91%). The presence of necrosis and absence of adenoma cells were significantly more prevalent among malignant group than among borderline and benign groups (P

Background Lobular endocervical glandular hyperplasia (LEGH) is a disease considered to be the origin of tumorigenesis of minimal deviation adenocarcinoma, which has characteristic expression in the gastric pyloric mucosa. It is difficult to diagnose by nuclear findings because of lower nuclear atypia. In this study, nuclei of endocervical (EC) and LEGH cells were digitized, and nuclear information was quantified from nuclear images and objectively evaluated using a computer. We examined whether it is possible to distinguish between EC and LEGH cells, which is difficult by human eyes. Methods Signal intensity, morphological features, Otsu thresholding technique and gray-level co-occurrence matrix (GLCM) features were calculated from nuclei of EC and LEGH cells on cytology microscopic images. Then, discriminant analysis was performed using the significant difference test and linear support vector machine (LSVM). Results GLCM features in LEGH cells were higher than those in EC cells. The nuclei of LEGH cells had a higher frequency of signal value pairs with a larger signal value difference than that of EC cells. Therefore, LEGH cell nuclei are thought to have more chromatin granules, and the chromatin is coarse and granular. Moreover, in the LSVM discriminant analysis, the accuracy of GLCM calculated using these features was 85.4%. Conclusion In this study, GLCM accurately demonstrated the nuclear chromatin distribution and coarseness. Discriminant analysis of EC and LEGH cells using GLCM features is useful.

Background Salivary duct carcinoma (SDC) is an uncommon and highly aggressive primary salivary gland neoplasm. Cytomorphologic features of SDC include cellular smears, nuclear atypia, prominent nucleoli, cribriform and papillary architecture, and background necrosis. The presence of oncocytic features has been described but not adequately characterized in the current literature. Method This study cohort consisted of 14 cases of histologically proven SDC with previous salivary gland fine needle aspiration (FNA). The cytologic material of each case was semi-quantitatively analyzed and evaluated for various cytomorphologic, architectural, and background features. Results Twelve SDCs were located in the parotid gland and two in the submandibular gland. In two cases the initial cytologic diagnoses was Warthin tumor or favor Warthin tumor. Moderate to marked degree of oncocytic changes were noted in all cases except one case. Nuclear atypia was variable with most cases exhibiting moderate to high-grade nuclear features, while four cases demonstrated low-grade nuclear cytomorphology. Cytoplasmic vacuolation was seen in nine cases and variable amount of background necrosis was observed in eight cases. Cribriform and papillary architecture was recognized in only six cases. Background lymphocytes were absent in all but one case. Conclusions Precise diagnosis of SDC based on cytomorphologic features alone can be challenging. Oncocytic change is one of the most consistent features observed in this case series and when associated with less pronounced cytologic atypia, can potentially lead to misdiagnosis as Warthin tumor. SDC should be considered in the differential diagnosis of oncocytic salivary gland neoplasms where precise diagnosis is not possible.

Background In the current version of The Bethesda System (TBS) for thyroid cytopathology, the atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category has an estimated risk of malignancy of 10% to 30%. Diagnostic criteria include presence of nuclear atypia, suggestive of papillary thyroid carcinoma (PTC), as well as other types of atypia, which can be seen with non-malignant entities. Aim of this study was to investigate differential outcomes of AUS/FLUS, based on specific morphologic criteria, and assess their respective malignancy risks. Methods From a total of 1233 patients undergoing thyroid FNAs between 2010 and 2014 at the University of Washington, 119 had AUS/FLUS without nuclear atypia, and 64 with nuclear atypia. Outcomes for patients with and without nuclear atypia (with the exception of 24 patients lost to follow-up) were evaluated and results were compared. Results 16/57 (28.1%) patients with AUS/FLUS and nuclear atypia subsequently had carcinomas on thyroidectomy, statistically higher than the 8/102 patients (7.8%, P = .001) without nuclear atypia. When comparing only patients who underwent surgery (n = 63), again those with AUS/FLUS and nuclear atypia had statistically higher rates of carcinoma (16/31, 51.6%), compared to those without (8/32, 25%; P = .0394). Overall, 24/159 (15.1%) of patients with AUS/FLUS had carcinoma on subsequent histology. Conclusion Malignancy rates for AUS/FLUS were in line with TBS estimated risks. However, our data demonstrate that the presence or absence of nuclear atypia is associated with different malignancy rates, suggesting the possibility that the AUS/FLUS category may best be split into two subcategories with different implied risks of malignancy.

BACKGROUND Pseudomyxoma peritonei (PMP) is a rare condition characterized by intraperitoneal accumulation of mucus due to mucinous neoplasia. The characteristic cytological feature of PMP in the ascites is abundant mucus with or without epithelial cell clusters. However, the prognostic significance of the presence of epithelial cell clusters has not been determined. This study aimed to determine the prognostic significance of epithelial cell clusters in the ascites of patients with PMP. METHODS Patients who were clinically and histopathologically diagnosed with PMP and who underwent intraoperative cytological examination of their ascites were included in this study. Cytological characteristics including mucus and epithelial cell clusters, nuclear atypia, and the presence of signet ring cells were investigated. Overall survival was compared based on the presence of epithelial cell clusters or nuclear atypia. RESULTS A total of 283 patients (199 women and 84 men) were investigated. The most common original site was the appendix (244 patients). Ninety patients (31.8%) had mucus without epithelial cell clusters (acellular mucin) while 193 (68.2%) had mucus with such clusters; 134 (69.4%) and 44 (22.8%) of these patients showed low-grade and high-grade nuclear features, respectively. Signet ring cells were detected in 15 patients (7.8%). The presence of epithelial cell clusters did not influence overall survival (P = .28); however, high-grade nuclear features and signet ring cell presence were significant negative prognostic factors (P < .001). CONCLUSION The presence of high-grade nuclear features or of signet ring cells should be carefully investigated in the cytological specimens of patients with PMP.

Due to the heterogenicity and morphological overlap among the broad spectrum of benign and malignant salivary gland lesions, cytopathology result interpretations can be challenging and variable even among the most experienced head and neck pathologist. There was no standardization of cytopathology result reporting until the recently proposed "Milan system for reporting salivary gland cytopathology" (MSRSGC). MSRSGC may offer more clarity and help minimize ambiguity, but surgeons, as part of multidisciplinary teams, do not only rely on the tiered stratification and risk of malignancy assessment. With only the MSRSGC reported, there may be critical information missing from the overall diagnostic evaluation of salivary gland masses. Cytopathologist evaluation, description of findings, and expert interpretation of the fine-needle aspiration cytology along with differential diagnosis can be critical pieces of information, that is, utilized in management discussions with patients and their families. This information needs to be included in every cytopathology interpretation in addition to the MSRSGC classification. In clinical practice, decisions concerning salivary gland tumor management are not based on single examinations but incorporate information from multiple sources including patient histories, clinical symptoms and signs, physical examinations, imaging studies, and when available, cytopathology. Additional cytopathology information will likely help to improve the utility and predictive power of MSRSGC, similar to Bethesda Classification and the predictive importance of nuclear atypia in indeterminate thyroid biopsy material for thyroid neoplasms.

We report a case of minimal deviation adenocarcinoma (MDA) of the uterine cervix showing varicolored cytopathologic features on Papanicolaou (Pap) smear, which may indicate features suggestive of lobular endocervical glandular hyperplasia (LEGH)-adenocarcinoma sequence. A 57-year-old woman presented with a profuse amount of watery vaginal discharge. Gynecological examination revealed a cervical mass with involvement of the right parametrium. Conventional Pap smear showed hypercellularity consisting of approximately 4 types of clusters as follows: (1) clusters showing a monolayered honeycomb sheet of endocervical cells with golden-yellow mucin and bland nuclei, (2) three-dimensional clusters showing varicolored mucin and irregular nuclear overlapping, (3) irregularly shaped clusters showing distorted chicken-wire-mesh appearance with noticeable protrusions of the nuclei and clear or faint varicolored cytoplasm, and (4) crowded clusters showing scarce mucin and nuclear atypia. The surgically resected uterus revealed LEGH-mimicking lesion with fused papillae and a cribriform pattern in the endocervix and many glands exhibiting gastric differentiation that invaded deeper areas of the stroma with a subtle stromal reaction. Compared with histologic findings, two types of clusters, the crowded cluster with scarce mucin and the cluster with distorted chicken-wire-mesh-type appearance, were considered as adenocarcinoma, and the latter was interpreted as a gastric-type adenocarcinoma. Three-dimensional varicolored type clusters showed atypical features, but insufficient atypical features compared with those of adenocarcinoma. Detection of clusters with varicolored mucin on conventional Pap smear may provide a clue for the early recognition of the malignant potential of LEGH on cytology. The chicken-wire-mesh type clusters may be a characteristic cytologic finding of MDA.

Subependymomas are slowly growing glial tumors, corresponding to WHO grade I. Few descriptions of the cytologic features of this neoplasm are available. This study describes the cytologic features of three subependymomas, as well as their differential diagnosis based on cytology. Three men, aged 52, 56, and 63 years, presented with headache. Magnetic resonance imaging revealed a nodular intraventricular mass in all three patients. Intraoperative squash cytology specimens from the three intraventricular tumors showed nodular clusters with microcystic changes. Nuclei were round to oval in shape, but showed no evidence of severe nuclear atypia or mitoses. Histological examination showed features of subependymoma. Squash cytology findings, including nodular clusters, mild cellular atypia, microcystic changes, and mucoid material, are useful in the rapid intraoperative diagnosis of subependymoma.

Introduction Whether true papillae without nuclear features of papillary carcinoma in thyroid fine needle aspirates should be diagnosed as atypia of undetermined significance (AUS) is unclear. Methods The results of all thyroid FNAs performed from 2014-2016 with corresponding resections as well as aspirates from 2000-2016 with a diagnosis of follicular variant of papillary carcinoma or Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) were reviewed. Results Papillae with fibrovascular cores were identified in 17 of 149 consecutive cases (11%), 3 of which had nuclear features of papillary carcinoma and were papillary carcinoma at resection. All 14 cases of papillae without nuclear features of papillary carcinoma were benign. Of 29 papillary carcinomas, papillae were identified in 8 (28%) and “swirls” were identified in 3 (10%) additional cases, all in cases of papillary carcinoma, NOS. Papillae and swirls were not identified in any cases of NIFTP (13 cases) or follicular variants of papillary carcinoma (15 cases). Conclusion True papillae are relatively common. Both papillae with nuclear atypia and swirls are highly specific for papillary carcinoma, NOS and are not seen in NIFTP. True papillae with fibrovascular cores but without cytologic features of papillary carcinoma are benign and should not be diagnosed as AUS.

Lobular endocervical glandular hyperplasia (LEGH) is an endocervical glandular hyperplastic lesion containing pyloric gland-like mucin, and has recently been recognized as a precursor lesion of malignant glandular lesions of the endocervix. The pyloric gland-like mucin contained in LEGH and gastric-type adenocarcinoma is observed as golden-yellowish by Papanicolaou staining. However, to our knowledge, the chronological course of the endocervical cytology of LEGH, eventually resulting in malignancy, has never been demonstrated to date. Here, we report two cases of gastric-type adenocarcinoma in situ (AIS) arising in LEGH, together with an analysis of their cytological course. In both cases, localization of mucin on the surface of glandular cell clusters was observed prior to nuclear atypia in endocervical cytology. In addition, the diagnosis of gastric-type AIS arising in LEGH was confirmed by pathological diagnosis of hysterectomy specimens in both cases. Histologically, all glandular cells of the LEGH without nuclear atypia contained a large amount of PAS-positive mucin. On the other hand, in atypical glandular cells, localization of the mucin on the luminal surface was observed, although mucin was abundant throughout the cytoplasm in some areas. Our cases show the course of acquirement of cytological atypia of LEGH, and indicate the significance of localization of mucin on the surface of glandular cell clusters as an early finding of the malignant transformation of LEGH in endocervical cytology. Our results indicate that the distribution of mucin in glandular cells should be analyzed together with nuclear atypia in the endocervical cytology of suspected cases of LEGH.

Background The objective of this study was to compare two cytological subcategories of thyroid nodules with Bethesda category III initial cytology. Methods This was a prospective study. All patients with thyroid nodules > 1 cm were eligible and 98 patients with category III cytology were selected. Cytology was subcategorized into architectural atypia only (AA, n = 45) and nuclear atypia (NA, n = 53). All patients underwent a second fine-needle aspiration (FNA). Only patients whose second cytology was benign and ultrasonography was non-suspicious were not referred for surgery. In these patients, the nodules were considered benign. Results The second FNA more frequently revealed “benign cytology” in the AA subcategory (44.4% vs. 24.5% in the NA subcategory). The second cytology suggested “follicular neoplasm” or was “suspicious for follicular neoplasm” (category IV) in 5 patients (11.1%) of subcategory AA and was “suspicious for malignancy” (category V) in 13 (24.5%) of subcategory NA. Finally, malignancy was diagnosed in 15.5% of cases of subcategory AA and in 41.5% of subcategory NA. Follicular carcinoma was more frequent in subcategory AA, while classical papillary carcinoma was more frequent in subcategory NA. Excluding cases of the noninvasive encapsulated follicular variant of papillary carcinoma, malignancy was diagnosed in 11.1% of patients of subcategory AA and in 35.8% of subcategory NA. Conclusions The results showed that subclassification of the Bethesda category III improves cancer risk prediction, with potential repercussions for clinical practice. Diagn. Cytopathol. 2017;45:604–607. © 2017 Wiley Periodicals, Inc.

Langerhans cell sarcoma (LCS) and quintuple cancers are extremely rare. In this report, a case of quintuple cancers including LCS was described. An 80-year-old man had squamous cell carcinoma of the nasal skin, colon and rectum adenocarcinomas, and T-cell/histiocyte-rich large B-cell lymphoma. As swelling of multiple submental lymph nodes was observed, fine-needle aspiration was carried out. Many large cells with high-grade nuclear atypia and abundant cytoplasm were observed. Lymphocytes and eosinophils were observed in the background. Although a malignant tumor was suspected, a definite diagnosis could not be made. In a biopsy sample, the tumor cells were positive for vimentin, CD68, S-100, CD1a, and CD163 and negative for epithelial, lymphocyte, and melanoma markers in immunohistochemistry. A diagnosis of LCS was made from the immunohistochemical findings and high mitotic rate with atypical forms. The patient died about 2 months after the first medical examination. Metastasis of LCS was confirmed in many organs by autopsy. LCS has a poor prognosis. In cases with the above-described cytological findings, LCS should be added to the list of differential diagnosis. The cytological findings presented here may be useful for determining appropriate clinical management such as staging of the disease and follow-up of the neoplasm. Diagn. Cytopathol. 2017;45:441-445. © 2017 The Authors Diagnostic Cytopathology Published by Wiley Periodicals, Inc.

Background The cytology of oral squamous cell carcinoma (SCC) is challenging because oral SCC cells tend to be well differentiated and lack nuclear atypia, often resulting in a false negative diagnosis. The purpose of this study was to establish practical cytological parameters specific to oral SCCs. Methods We reviewed 123 cases of malignancy and 53 of non-neoplastic lesions of the oral mucosa, which had been diagnosed using both cytology and histopathology specimens. From those, we selected 12 SCC and 4 CIS cases that had initially been categorized as NILM to ASC-H with the Bethesda system, as well as 4 non-neoplastic samples categorized as LSIL or ASC-H as controls, and compared their characteristic findings. After careful examinations, we highlighted five cytological parameters, as described in Results. Those 20 cytology samples were then reevaluated by 4 independent examiners using the Bethesda system as well as the 5 parameters. Results Five cytological features, (i) concentric arrangement of orangeophilic cells (indicating keratin pearls), (ii) large number of orangeophilic cells, (iii) bizarre-shaped orangeophilic cells without nuclear atypia, (iv) keratoglobules, and (v) uneven filamentous cytoplasm, were found to be significant parameters. All malignant cases contained at least one of those parameters, while none were observed in the four non-neoplastic cases with nuclear atypia. In reevaluations, the Bethesda system did not help the screeners distinguish oral SCCs from non-neoplastic lesions, while use of the five parameters enabled them to make a diagnosis of SCC. Conclusion Recognition of the present five parameters is useful for oral SCC cytology. Diagn. Cytopathol. 2017;45:406-417. © 2017 Wiley Periodicals, Inc.

Endometriosis commonly involves the pelvis, but may also present as a palpable mass in extrapelvic sites, such as the abdominal wall or inguinal region, where it can be evaluated by fine needle aspiration (FNA). In this report, we illustrate the findings seen in seven cases of endometriosis diagnosed by FNA in patients with a chief complaint of pain associated with an abdominal wall or pelvic mass, occurring in a setting of prior pelvic surgery. The most common previous surgery was Cesarean section (n = 6), followed by hysterectomy (n = 2), and hernia repair (n = 1). In all cases, cytologic examination revealed a glandular component composed largely of orderly fragments of cohesive epithelial cells, a spindle cell stromal component presenting either as loosely organized tissue fragments or single cells, and rare hemosiderin-laden macrophages. Four cases showed focal cytologic atypia in the glandular component with extreme nuclear atypia identified in two of these cases. Atypical features included nuclear crowding and disorganization, nuclear enlargement, hyperchromasia with irregular chromatin distribution and anisonucleosis, raising the possibility of a coexistent malignancy and recommendation for excision. Although malignancy was not identified in follow-up surgical excision specimens, the wide range of cytomorphologic changes that can be seen in FNA specimens of endometriosis should be recognized. Diagn. Cytopathol. 2017;45:359-363. © 2016 Wiley Periodicals, Inc.

Sarcomatoid carcinoma is rarely found in pleural or pericardial fluid, with very few cases published to date. Here, we describe a 59-year-old female who presented with cough persisting for 5 months. Chest CT scan revealed a 6.0 cm cavitary mass in the left lung base with bulky mediastinal and hilar lymphadenopathy. An additional 1.2 cm right adrenal mass was seen and was suspicious for metastatic disease. The patient developed dyspnea, tachycardia, pleuritic chest pain and generalized weakness and was admitted to the hospital. She was found to have pleural and pericardial effusions, which were drained and sent to cytology. The fluid revealed enlarged highly pleomorphic malignant cells, some displaying multinucleation with irregular nuclear borders, coarse chromatin and prominent nucleoli. Tumor cells were positive for CK7 and Vimentin and negative for MOC-31, Ber-EP4, B72.3, Sox10, Melan-A, TTF-1, Napsin-A and CK20. A concurrent surgical biopsy of the tumor mass displayed immunopositivity for AE1/AE3 and CAM5.2. The tumor was negative for p40, TTF-1, calretinin, D2-40 and STAT6. A diagnosis of sarcomatoid carcinoma with giant cells and spindle cells was rendered. Sarcomatoid carcinomas of the lung are very uncommon consisting of 1% of non-small-cell lung carcinomas and are even more unusual in cytology specimens. Despite its rarity, it is important to keep this entity in mind in the differential diagnosis of a fluid specimen with bizarre nuclear atypia and the above staining pattern.

Background All malignant tumors may spread throughout the pleural, peritoneal, and pericardial cavities. The presence of tumor cells in serosal fluid is a poor prognostic indicator. It may be difficult to differentiate nuclear atypia of mesothelial cells due to injury of serosal surfaces from mesothelioma or malignant epithelial tumor cells. Epithelial and mesothelial immunohistochemical markers can be used in such conditions. The aim of this study was to evaluate the expression of two immunohistochemical markers (MOC-31 and EZH2) in serosal effusions. Methods The study included a total of 142 patients diagnosed with benign or malignant cytology between January 2012 and April 2014. MOC-31 and EZH2 were applied to the cell blocks of 53 patients with benign cytology and 89 patients with malignant cytology determined based on the clinical, radiological data, histopathology diagnosis, and clinical follow-up in the absence of any surgical material of the patient in the hospital archive system. Results None of the benign cases showed MOC-31 and EZH2 expression, although these markers were positive in 96 and 93% respectively of the malignant cases. Conclusion In conclusion, it could be considered cost-effective to use a double immunohistochemical antibody kit for these two markers, MOC-31 membranous and EZH2 nuclear staining, in the diagnosis of malignant effusions. Diagn. Cytopathol. 2017;45:118–124. © 2016 Wiley Periodicals, Inc.

Well-differentiated fetal adenocarcinoma (WDFA) of the lung is a rare variant of adenocarcinoma with an unusual morphology. Although the histologic features of this rare neoplasm have been well established, there is a deficit in the literature with regards to its discrete cytomorphologic features. We report the fine needle aspiration (FNA) findings of a case of this unusual malignancy in a 44-year-old man with an incidental lung nodule. FNA revealed three-dimensional clusters of epithelial cells with scant cytoplasm, hyperchromatic nuclei that are associated with an extracellular metachromatic matrix. The original cytology report was signed out as an epithelial neoplasm favor adenoid cystic carcinoma. Consequently, a wedge resection of the lung was done and the histologic diagnosis was WDFA of the lung. The findings of minimal nuclear atypia in association with focally abundant spheres of extracellular matrix can mimic adenoid cystic carcinoma. WDFA has good prognosis and therefore, pre-operative cytologic diagnosis is critical to clinical management. We present the cytomorphologic features of this neoplasm with particular emphasis on a potential diagnostic pitfall of this rare entity. Diagn. Cytopathol. 2016;44:917-920. © 2016 Wiley Periodicals, Inc.

Background Choroidal and ciliary body melanomas divide into two approximately equal groups. Local therapy cures one group while the other metastasizes and proves lethal. Monosomy 3 strongly associates with aggressive behavior. We analyzed a series of choroidal and ciliary body melanomas to describe the cellular features and to compare them to monosomy 3 status using the latter as a surrogate for survival. Methods One hundred eleven specimens met the study's inclusion criteria. Following ThinPrep processing, samples were analyzed for cellular features including: cell type, nuclear grade, tumor infiltrating lymphocytes, and the presence of necrosis and melanin. FISH analysis for monosomy 3 was performed on ThinPrep slides using a threshold of 20% monosomic cells per 200 melanoma cells. Results Seventy-two tumors (65%) had a mixed cell type while spindle cell type and epithelioid cell type occurred in 37 (33%) and 2 (1.8%), respectively. Seventy-five tumors (68%) had Grade 2 nuclear atypia. Monosomy 3 occurred in 57 tumors (51%). Significantly more tumors with Grade 3 nuclei had monosomy 3 (79% vs.43%, P = 0.002) and metastases (29% vs. 8%, P = 0.01). None of the 11 pure spindle cell tumors with Grade 1 nuclei metastasized or had monosomy 3. Conclusions Uveal melanoma has a relatively consistent cellular appearance, characterized by a mixed cell pattern and no more than moderate nuclear atypia. This consistent appearance aids in the cellular diagnosis but limits prognostication using cellular features. Cellular features significantly associate with monosomy 3 status only in the minority of tumors at the extremes of the morphologic spectrum. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Biphenotypic sinonasal sarcoma (BSNS) is a rare low-grade spindle cell sarcoma that predominantly affects middle-aged women with multiple tumors in the sinonasal tract. BSNS shows biphenotypic expression of neural and myogenic markers on immunohistochemistry (IHC) with a specific chimeric PAX3-MAML3 fusion. The cytological features of BSNS have so far not been reported. Here, we describe a case of BSNS including findings of imprint cytology, histology, IHC, and genetic analysis. A 30-year-old woman presented with a nodular tumor that completely occupied the ethmoid sinus. The tumor was resected and submitted for imprint cytology, which revealed relatively bland spindle tumor cells that had mildly enlarged oval to spindle-shaped nuclei with fine nuclear chromatin and a thin nuclear rim in a clear background. Nucleoli were inconspicuous and there was no significant nuclear atypia and pleomorphism. These cytological findings were consistent with the histology of low-grade spindle cell sarcoma in BSNS. On IHC, the tumor cells were focally positive for S-100 protein and α-smooth muscle actin; nuclear β-catenin expression was also seen. PAX3 split signals were detected in 52% of tumor cells by fluorescence in situ hybridization. Reverse transcriptase-polymerase chain reaction also identified a chimeric PAX3-MAML3 fusion gene. Based on these findings, we diagnosed the tumor as BSNS. Our findings revealed that a relatively bland spindle cell cytology with a clear background is a characteristic feature of BSNS. BSNS should therefore be differentiated from benign and bland-appearing malignant spindle cell tumors and the combination of cytology, histology, IHC, and genetic analysis facilitates the diagnosis of BSNS.

Ciliated muconodular papillary tumors (CMPTs) of the lung are rare, likely benign neoplastic lesions. Here we describe a case of a CMPT, focusing on its cytologic features, which to our knowledge have not been reported previously. Owing to dull back pain, a 69-year-old male non-smoker underwent CT, which revealed a 1.3 × 1.3-cm solid nodule in the peripheral field of the left lower lung lobe. A wedge resection of the nodule was performed, with the provisional diagnosis being primary lung cancer. Macroscopic examination of a resected specimen showed a 1.2-cm grayish nodule. Touch imprint smear cytology revealed ciliated columnar cells and mucous cells, as well as abundant extracellular mucin on inflammatory background of lymphocytes and histiocytes. Histologic examination revealed a nodular papillary tumor composed of ciliated columnar cells, mucous cells, and basal cells surrounded by a mucin pool. No nuclear atypia or mitotic figures were identified. The final diagnosis was CMPT. The postoperative course was uneventful, with no recurrence at 8 months after surgery. Although a CMPT is a rare lung tumor, it should be considered when cytological or histological examination of a solitary peripheral lung nodule shows non-atypical ciliated cells and mucous cells surrounded by mucin.

Background The cytomorphological features in the distinction between phyllodes tumour (PT) and fibroadenoma (FA) on fine needle aspiration biopsy (FNAB) remains challenging because of the biphasic nature of these lesions and the rarity of PT. Methods FNAB smears of histologically confirmed PT (N = 26) and FA (N = 78) cases were retrieved from a retrospective database interrogation from the Department of Cytology/Tissue Pathology, ICPMR Pathology West (Cerner Millennium) in Westmead Hospital. For each case, two smears were selected, de-identified and independently reviewed by four observers comprising two cytologists and two cytopathologists. Cytological parameters examined included detailed evaluation of smear cellularity, epithelial and stromal components as well as the smear background. Results The cytological features of moderate to marked stromal cellularity and stromal nuclear atypia were more evident in PT than in FA, identified by three out of four observers. The epithelial characteristics, presence of macrophages, multinucleated giant cells and blood vessels showed no statistically significant differences in the distinction between the two lesions. Conclusion The results of this study indicate that in all of the cytological features assessed for PT and FA, no single cytological feature was found to be statistically significant in identifying PT across all observers. This reflects the overlap of cytological features seen in these lesions. FNAB cytology cannot reliably distinguish FA and PT.

Background To determine the frequency of squamous cell change associated with endometrial carcinoma, to evaluate the relationship between squamous cell change and clinicopathological features, and to assess cytological findings for squamous cells with and without nuclear atypia in endometrial smears. Methods In 103 cases of endometrioid adenocarcinoma of the endometrium having both histological and cytological specimens, the frequencies and relationships between the presence and absence of squamous cell changes were evaluated, as were the clinicopathological features of such changes. In endometrial smears, squamous cells with and without nuclear atypia were clinicopathologically assessed. Results Squamous cell changes were found in 58.3% of cases that had both histological and cytological preparations. There were no significant differences between the group with squamous cell changes and the group without in any of the clinicopathological features. In the cytological smears, 70.0% of the 60 cases that showed squamous cell changes in both preparations did not have nuclear atypia of squamous cells, while 30.0% of those cases had atypia. The group of cases with squamous cells without atypia tended to be better differentiated than the group with atypia. Vessels were permeated significantly more often in the group with atypia than in the group without. Conclusions Our data suggest the importance of observing squamous cells in endometrial cytology, especially concerning findings on nuclei with vs without atypia, when endometrial carcinoma is suspected. Diagn. Cytopathol. 2015. © 2015 Wiley Periodicals, Inc.

Low-grade cribriform cystadenocarcinoma of the parotid gland is rare malignancy that is classified as a variant of cystadenocarcinoma. In routine cytologic slides from fine-needle aspiration of a parotid gland, we found several pseudopapillary clusters comprising mucus-producing cells. They included a few tumor cells having three-dimensional nuclear atypia and slight hyperchromatism, although most of the tumor cells showed bland nuclei. Our initial cytological diagnosis was: "Indeterminate. Uncertain whether cystadenocarcinoma or cystadenoma." The subsequent histological diagnosis was low-grade cribriform cystadenocarcinoma. Immunohistochemical staining showed diffuse and strong reactivity for S-100; tumor nests that were rimmed by p63(+) cells, which suggests intraductal proliferation. Here, we report cytomorphological findings of this case, and discuss cytological and immunohistochemical distinctions between low-grade cribriform cystadenocarcinoma and other salivary gland tumors, including a review of the literature.

Background Stratified mucin-producing intraepithelial lesion (SMILE) is an uncommon variant of in situ carcinoma of the cervix. This study aimed to identify the cytologic features of SMILE since these have not been well documented previously. Methods The study group comprised 34 consecutive cases of SMILE encountered at a single institution in which a corresponding Papanicolaou smear, taken up to 12 months before histologic diagnosis, was available for review. The presence of associated cervical neoplastic lesions including cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive carcinoma was recorded. The linear extent and distribution of the SMILEs was also noted. Results Most Pap smears had been reported to show possible or definite high-grade CIN although 3 cases reported the presence of a high-grade glandular abnormality. No case had a prospective cytologic diagnosis of SMILE. Histology revealed concurrent CIN and/or AIS in all cases, and 1 specimen (3%) showed invasive adenocarcinoma. Following smear review, 23 of the 31 cases that included endocervical material showed recurrent cytologic features that appeared consistent with SMILE. These included three dimensional cell clusters with nuclear stratification and crowding, mild nuclear atypia, cytoplasmic vacuoles, mitotic figures, and apoptosis. Conclusion SMILE is almost always associated with additional HPV-related neoplastic lesions although only one patient (3%) had invasive carcinoma, a lower rate than recorded in other studies. Consistent cytologic features associated with SMILE were identified but these were relatively subtle. However, increased awareness of these features may permit prospective diagnosis and this could influence patient management. Diagn. Cytopathol. 2016;44:20–25. © 2015 Wiley Periodicals, Inc.

Primary mucinous carcinoma of skin is an uncommonly documented tumor, especially on fine-needle aspiration cytology (FNAC) smears. A 58-year-old gentleman presented with a recurrent swelling over his right zygoma. Earlier, he had undergone surgical resection at the same site, on two occasions, 4 years back. FNAC smears from the recurrent nodule displayed clusters and singly scattered relatively monomorphic, polygonal to plasmacytoid cells with mild nuclear atypia and moderate to abundant cytoplasm, including focal intracytoplasmic vacuoles. At places, tumor cells were arranged around psammoma bodies against a background of mucinous material. Histopathological sections from the subsequent tumor resection revealed tumor cells arranged in the form of islands, nests, cribriform, and papillary arrangements amidst mucinous stroma, along with focal psammomatous calcification, consistent with a recurrent mucinous adenocarcinoma. On immunohistochemistry, tumor cells were diffusely positive for CK 7, estrogen receptor (ER), and progesterone receptor (PR), while negative for CDX2, CK20, and TTF1. Diagnosis of a recurrent mucinous carcinoma of skin was offered. Patient underwent adjuvant radiotherapy for achieving better loco regional clearance and is disease-free, 4 months after. FNAC is a useful diagnostic tool for timely identification of mucinous carcinoma of skin, including recurrent lesions. Psammomatous calcification can be identified within this uncommon tumor, in recurrent lesions. While surgical resection remains the treatment mainstay, immunohistochemical expression of ER and PR in this tumor perhaps could have therapeutic impact, especially in recurrent cases.

Squamous-lined cysts (SLC) in the pancreas are rare and include lymphoepithelial cysts (LEC), dermoid cysts (DC), and epidermoid cysts in heterotopic spleen (EC). Previously only rare case reports and small case series have been published describing the FNA findings in these entities. The departmental archives were searched for surgically excised SLC from the pancreas. Twenty-five specimens were identified: 20 LEC, four EC, and one DC. Eight corresponding FNA specimens taken prior to resection were identified and available for review: seven LEC and one EC. A junior and senior pathologist reviewed the cases individually and then together for consensus. On morphological review, all lesions contained single nucleated and anucleated mature squamous cells, macrophages, and varying amounts of lymphocytes. Benign squamous fragments were found in half of all specimens. Amorphous debris was found in all cases. Keratin was found in all but two cases and its appearance varied among cases. Half of all cases contained cholesterol crystals. No nuclear atypia or necrosis was noted. Inspissated mucin, a potentially misleading finding, was seen in three cases. The most important goal in evaluating pancreatic cystic lesions is to exclude a mucin-producing neoplasm. If features of a SLC are present, the differential diagnosis should include LEC, DC, and EC. Only 38% (3/8) cases had the most specific features of an SLC present (squamous fragments, cholesterol crystals, keratin, and squamous cells), which suggests that most cases will not be specifically identified on FNA even by experienced cytopathologists.

Intraductal tubulopapillary neoplasm (ITPN) of the pancreas, a novel entity included in the World Health Organization 2010 classification, accounts for

Adenoid cystic carcinoma (AdCC) is a distinct type of carcinoma, and cytological examination has been recognized as a useful tool in its diagnosis. Dedifferentiation is defined as the abrupt transformation of a low-grade tumor into a tumor with high-grade components. Albeit extremely rare, dedifferentiated AdCC has been reported: however, the cytological features of this tumor have not been documented. We observed a case in which a 66-year-old Japanese male had stenosis and thickness of the lower tracheal and bronchial walls. Cytological smears of a bronchial brush specimen revealed features typical for low-grade AdCC. However, a few cohesive epithelial cell clusters composed of large, atypical polygonal cells with large nuclei and conspicuous nucleoli also were present. This component was considered to represent dedifferentiated carcinoma. Histopathological study of the resected bronchial tumor revealed dedifferentiated AdCC. The cytological diagnosis of conventional low-grade AdCC is straightforward in most cases, although extremely rare, dedifferentiated carcinoma can occur within the conventional AdCC, and detection of a dedifferentiated component is possible in a cytological specimen because of obvious nuclear atypia. Therefore, careful observation is needed because cytologic diagnosis of dedifferentiated AdCC can help expedite treatment of this highly aggressive tumor.

Adequately cellular and representative fine-needle aspirates (FNAs) of breast have a high diagnostic accuracy. There is, however, a recognized category designated as “gray zone” where a definitive diagnosis cannot be reached. We reviewed our experience in this category to identify useful diagnostic parameters. Twenty-four such FNAs with surgical follow-up were retrieved from AUBMC files (2003–2009). Cytology slides were reviewed blindly. All cases were females, 29–73 years. There were three erroneous and 21 inconclusive diagnoses. The majority (15) was invasive adenocarcinomas: two cribriform, four tubular, one lobular, and eight not otherwise specified. The remaining cases were papillary and fibroepithelial tumors (three each), ductal carcinoma in situ, cribriform (two), and one adenomyoepithelioma (AME). Useful diagnostic features included: (1) Biphasic cell population with focal nuclear atypia and intranuclear and cytoplasmic vacuolar inclusions (AME). (2) Complex clusters of epithelial cells with cribriform architecture (cribriform carcinoma). (3) Rigid tubular epithelial structures with abrupt change in diameter, ending in pointed tips with abnormal branching (tubular carcinoma). (4) Cellular stromal fragments (fibroepithelial tumors). (5) Papillary fibrovascular cores, columnar cells, and three-dimensional papillary epithelial fragments (papillary tumors). Myoepithelial cells classically described in benign aspirates were not always a discriminatory factor. The “gray zone” in breast FNA is usually due to overlapping cytologic features of some benign and malignant lesions. Useful distinguishing cytologic features are described. Diagn. Cytopathol 2014;42:405–415. © 2013 Wiley Periodicals, Inc.

Controversy exists regarding the validity of follicular lesion of undetermined significance (FLUS), an indeterminate diagnostic category of The Bethesda System for Reporting Thyroid Cytopathology (BSRTC). According to BSRTC, FLUS carries a 5-15% risk of cancer. This study was designed to determine if cytomorphology could stratify FLUS into subgroups with different risks of malignancy. Reports of 127 consecutive FNAs reported as FLUS with subsequent tissue diagnoses were evaluated for the presence of various cytologic features and the results were correlated with histological diagnoses. FLUS cases with focal nuclear atypia (nuclear overlap/crowding, nuclear grooves/membrane irregularities, nuclear enlargement, and/or nuclear pseudoinclusions) were more frequently malignant on excision whereas those with architectural atypia (microfollicles) were more often benign on excision (P < 0.05). The presence of any one or more of these nuclear features increased the risk of carcinoma in subsequent thyroid resection. Papillary carcinomas predominated in excised FLUS cases with focal nuclear atypia whereas most FLUS with architectural atypia were adenomas or hyperplastic nodules on histological evaluation. BSRTC recommends that thyroid aspirates containing follicular cell nuclear and/or architectural atypia insufficient for a diagnosis of suspicious for follicular neoplasm, suspicious for malignancy or malignant be classified as FLUS. Our findings indicate that FLUS cases with focal nuclear atypia carry a risk for malignancy that is substantially higher than that assigned to FLUS and are best classified as suspicious. FLUS cases lacking these atypical nuclear features have a risk for malignancy that approximates the risk BSRTC has assigned to FLUS.

Metanephric adenoma of the kidney is an uncommon benign epithelial neoplasm with only a small number of reports that describe its cytologic features. We describe two additional cases of metanephric adenoma diagnosed on fine-needle aspiration biopsy and review the available literature. Our cases showed similar cytology and were composed of cellular smears with numerous clusters of small, oval to round cells arranged in a microfollicular pattern and papillary configurations. The tumor cells had scant cytoplasm, fine chromatin and absent nucleoli. Psamomma bodies, nuclear atypia, cellular cpleomorphism, necrosis, and mitoses were absent. Because of the rarity of this tumor and the common cytologic features it shares with other lesions, including malignant tumors such as Wilms' tumor and papillary renal cell carcinoma, awareness of the cytologic features of metanephric adenoma may aid in avoiding a diagnosis of malignancy, especially preoperatively, and in guiding the proper management for the patients.

Pulmonary neuroendocrine tumors (PNET) are histologically subclassified into typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell carcinoma (SCLC). The criteria for subclassification in cytological specimens are not well defined. In this study, we reviewed histologically confirmed 18 TC, 8 AC, 10 LCNEC, and 10 SCLC cytologic specimens from 45 patients. The following features were reviewed: small clusters, geographic sheets, trabecular structures, pseudo-rosettes, single cells, doublets, triplets or short cords, papillary-like structures, capillary vasculatures, necrosis, smear background, cell size, cell pleomorphism, amount of cytoplasm, plasmacytoid cells, spindle cells, nuclear atypia, molding, palisading and smearing, chromatin textures, nucleoli, and mitotic figure count. Based on our results, geographic clusters and necrosis were often seen in LCNEC and SCLC; while AC only showed scattered single cell necrosis. TC and AC commonly exhibited trabecular structures. Papillary-like structures and capillary vasculature were only present in TC, AC, and LCNEC. Cells forming doublets, triplets, and short cords were more commonly seen in SCLC and rarely seen in other entities. Plasmacytoid and spindle cells were only seen in TC and AC. Nuclear smearing was not identified in TC, rare in AC, focally present in LCNEC and obvious in SCLC. Mitotic figures were nearly absent in TC, ≤5/10 HPF in AT, and ≥10/10 HPF in SCLC. LCNEC showed a wide span of mitotic count ranging between 2 and 16/10 HPF. In this study, we propose a set of cytological features that are essential for subclassification of PNETs in cytologic specimens. Diagn. Cytopathol. 2013;41:689–696. © 2013 Wiley Periodicals, Inc.

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.

The Bethesda 2007 Thyroid Cytology Classification defines follicular lesion of undetermined significance as a heterogeneous category of cases that are not convincingly benign nor sufficiently atypical for a diagnosis of follicular neoplasm or suspicious for malignancy. In our institution, we refer to these cases as indeterminate, and they are further sub-classified into two: (1) low cellularity with predominant microfollicular architecture and absence of colloid (IN(a)) and (2) nuclear features not characteristic of benign lesions (nuclear atypia) (IN(b)). We reviewed these indeterminate cases to document the follow-up trend using this two-tier classification. A search of the cytology records was performed for the period between January 2008 and June 2009. All thyroid fine-needle aspiration (FNA) cases were reviewed and the ones diagnosed as indeterminate were identified. Correlating follow-up FNA and/or surgical pathology reports were reviewed. The percentage of cases showing a malignancy was calculated. One hundred and seventy-one indeterminate cases were identified, representing 2.8% of the 6,205 thyroid FNA cases examined during the time under review (107 IN(a), 64 IN(b)). Records of follow-up procedures were available in 106 (61%) cases. Malignancy was identified in 27% of all indeterminate cases. This was disproportionately more in the IN(b) (56%) compared to the IN(a) (7%) cases. A diagnosis of "IN(a)" does not carry the same implication as that of "IN(b)". The IN(b) category needs a more aggressive follow-up than the IN(a) category and may justify an immediate referral for lobectomy. Despite the vague morphologic criteria for this diagnostic category, the indeterminate rate remains relatively low and falls within the NCI recommendation (

Warty (condylomatous) carcinoma (WC) is a rare specific variant of invasive squamous cell carcinoma that shows hybrid features of condyloma with invasive cell carcinoma. As compared with conventional squamous cell carcinoma, WC tends to run a less aggressive clinical course. A case is presented here in which squash smears of a penile foreskin tumor in a 65-year-old male revealed small cohesive clusters and sheets of tumor cells in papillary configurations. The neoplastic cells were polygonal to elongated and contained oval nuclei, coarse chromatin pattern, and distinct nucleoli. Nuclear pleomorphism and loss of nuclear polarity were observed. Characteristically, there were also many koilocytes demonstrating mild to moderate nuclear atypia and perinuclear cytoplasmic halos. A cytologic diagnosis of a verruciform penile tumor was suggested. Histologic examination of the tumor showed a hyper-parakeratotic arborizing papillomatous growth with thin fibrovascular cores and the tips were variably rounded or tapered. Obvious koilocytic cytopathic change, nuclear pleomorphism, and focal stromal invasion were observed. Immunohistochemically, the tumor cells showed diffuse and strong membranous staining for cytokeratin (AE1/AE3) while the MIB-1 and p53 immunoreactive cells were confined to the basal areas of the papillae. No lymphovascular invasion was detected in D2-40 or elastic Van-Gieson stains. On the basis of the overall features, we confirmed a final diagnosis of penile WC. We demonstrated here for the first time the cytopathological features of penile WC with emphasis on differential diagnostic considerations. Diagn. Cytopathol. 2010;38:841–845. © 2010 Wiley-Liss, Inc.

Cytology is the only useful tool in the detection of malignant mesothelioma (MM) at an early stage. No other methods, such as immunocytochemistry or electron microscopy, are available to distinguish MM from reactive mesothelial cells (RMC). Some objective analysis of cytology specimens is necessary. On the basis of our case review and cytological features described in previous articles, we developed a scoring system for malignant mesothelioma (SSMM) of effusion cytology to distinguish MM cells from RMC. Mesothelioma cells in effusions from 22 patients (20 pleural and 2 peritoneal mesotheliomas) were compared with RMC from 20 patients without obvious tumor cells and 50 effusions containing metastatic carcinoma cells. The SSMM is based on characteristic features of mesothelial and malignant cells. The total achievable score is 10 points: one point each is given for variety of cell size, cyanophilic cytoplasm with villosity/windows/bleb, sheet-like arrangement, mirror-ball-like cell clusters, nuclear atypia, and cannibalism, respectively. Further two points each are ascribed for acidophilic large nucleoli and multinucleated cells with more than eight nuclei. The total score for each of the 22 mesotheliomas was more than 5 points. On the other hand, all RMC and the 50 metastatic carcinoma cases scored less than 3 points, aside from two cases that were treated with OK432. No single characteristic feature was observed to be consistent within the 22 mesotheliomas analyzed. Ancillary use of immunocytochemistry, such as podoplanin (D2-40) and calretinin, supported the diagnostic accuracy of the SSMM. SSMM is useful for the differential diagnosis of MM.

Breast carcinoma is a heterogeneous disease. It can be classified into phenotypes based on the expression of certain proteins, with distinct differences in prognosis. The basal phenotype is associated with worse prognosis and it still remains without specific treatment. However, there is currently no international consensus on the cytological criteria that could predict this phenotype. The purpose of the study was to evaluate the cytological criteria in fine-needle aspiration biopsy and to identify their association with the basal phenotype of breast carcinoma. Fine-needle aspiration biopsy specimens and tissue sections (mastectomy specimen) from 74 cases of high-grade invasive ductal breast carcinomas were consecutively retrieved from the files of three institutions. Breast carcinomas were studied using the tissue microarray technique, being classified into phenotypes: luminal A, luminal B, HER2 overexpression, and basal. The cytological criteria for all cases were reviewed blindly by two pathologists according to five cytological criteria: cellularity, cell pattern, presence of necrosis, nucleoli, and nuclear atypia. Exact Fisher test was used to test the association between cytological criteria and the phenotypes of breast carcinoma. Necrosis was present in 64.7% of basal breast carcinomas, and 31.1% of nonbasal breast carcinomas, and that result was statistically significant, showing an odds ratio (OR) of 3.80. The basal phenotype, compared with the luminal A, showed more necrosis (OR = 6.97), present/prominent nucleoli (OR = 8.18), and cellularity more frequently (OR = 18.03). Necrosis, as well as present/prominent nucleoli and abundant cellularity are criteria more frequently associated to the basal phenotype of breast carcinoma. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc.

Identification of Hürthle cells on fine-needle aspiration (FNA) of the thyroid leads to a wide differential diagnosis including benignand malignant entities. We report the cytological and histological findings of a patient with an oncocytic variant of papillary thyroid carcinoma (PTC) with concurrent Hashimoto's thyroiditis. FNA revealed a lymphoplasmacytic infiltrate with Hürthle cells demonstrating abnormal chromatin patterns, nuclear enlargement, pleomorphism, intranuclear cytoplasmic invaginations, and foci of papillary aggregates. Because of the degree of nuclear atypia and suspicion for concurrent papillary thyroid carcinoma, a total thyroidectomy was performed revealing a papillary arrangement of Hürthle cells with classic PTC nuclear changes and associated Hashimoto's thyroiditis. This report discusses cytopathological features of a rare variant of PTC (oncocytic subtype) in the background of Hashimoto's thyroiditis. We also briefly discuss the differential diagnosis and diagnostic pitfalls of Hürthle cell lesions, with a review of the literature.

The diverse morphological features encountered in pleomorphic adenoma (PA) may cause diagnostic errors in fine needle aspiration cytology (FNAC). The present study was performed to evaluate the variations in the cytological features of pleomorphic adenoma and to assess the efficacy of FNAC in its diagnosis. Fifty cases diagnosed as PA on FNAC were retrieved from the records of the Pathology Department. Cytologic smears and sections were reviewed and the cytologic diagnoses were compared with the definitive histologic diagnoses. In cases correctly diagnosed on aspiration, morphological variables like patterns of the epithelial component, type and extent of the mesenchymal matrix, metaplastic cells, hyaline globules, cystic change, giant cells, crystalline deposits, nuclear inclusions/grooves, and nuclear atypia were evaluated. The extreme diversity in morphologic features seen in histologic sections was reflected in the smears of PA. Metaplastic changes were observed more frequently in sections, while nuclear changes like inclusions/grooves were more commonly seen in smears. Other morphological features like cylindromatous pattern, giant cells and crystalline deposits were observed with equal frequency in smears and sections. Cytohistologic agreement was present in 45 of the 50 cases (90%). In 5 cases diagnosed as pleomorphic adenoma on FNAC, the histology revealed 1 case each of schwannoma, perineurioma, ectomesenchymal chondromyxoid tumor of tongue, adenoid cystic carcinoma and mucoepidermoid carcinoma. FNAC is a fairly accurate pre-operative procedure for the diagnosis of PA. The cytopathologist needs to be aware of the cytologic variations in pleomorphic adenoma so as to avoid diagnostic errors.

Nodular fasciitis (NF) is a benign, proliferative lesion of myofibroblasts. The most common site of the lesion is in the upper extremities or trunk. NF in the head and neck is next in frequency and is the most common site in infants and children. In adults, NF in the submandibular region is very rare. We report a case of a 53-year-old man with a submandibular mass, rapidly growing for 10 days. Cytologic findings revealed a few sheets or clusters of small, uniform spindle cells. The uniform spindle cells had centrally located round to ovoid nucleus, but there were no nuclear atypia and atypical mitosis. There were focally loose stroma but we could not find chondroid or myxoid components. A partial parotidectomy was performed. We describe a case of NF in the submandibular region, adjacent to the parotid gland and review the clinical, cytologic, histologic, and immunohistochemical features of NF.

Pineal parenchyma tumor of intermediate differentiation (PPTID) is a very rare intracranial tumor, and pathological investigation limited to immunohistological and ultrastructural analyses have been published to date. Although intraoperative cytology is one of the important approaches for initial diagnosis in brain tumors, no or little studies on cellular morphology of PPTID have been demonstrated due to its rarity. We report here cytological features of PPTID obtained from stereotactic surgical specimens in a case of 27-year-old female manifested by dizziness and diplopia. Brain MRI revealed an unhomogeneously enhanced, large-sized tumor (56 x 52 x 60 mm) mainly located in the pineal region expanding from the midbrain to superior portion of the cerebellum and the fourth ventricle. Squash cytology showed increased nucleocytoplasmic ratio, hyperchromatic nuclei, and small rosette-like cell cluster but cellular pleomorphism was mild to moderate and necrotic background was not observed. Histology showed high cellularity, moderate nuclear atypia, and small rosette formation but neither bizarre tumor cells nor necrosis was present. Mitotic counts were very low (less than 1 per 10 high-power fields) and the MIB-1 labeling index was relatively high (10.1%). Tumor cells were immunohistochemically positive for neural markers such as synaptophysin, neurospecific enolase but not for glial fibrillary acidic protein or S-100. In some parts, cells were strongly reactive for neurofilament protein. Taken together, we made a final diagnosis of PPTID. This is the first presentation of cytological analysis by squash preparation that gives an important clue to accurate diagnosis of pineal parenchymal tumor and to understand its malignant potential.

Oncogenic (tumor-induced) osteomalacia is a rare paraneoplastic syndrome of phosphate wasting that is frequently associated with phosphaturic mesenchymal tumor (PMT). As the cytologic features of this tumor apparently have not been reported, we describe the fine-needle aspiration (FNA) findings for PMT that arose from the gluteal soft tissue in a patient with hypophosphatemia and multiple fractures secondary to osteomalacia. Smears from the computerized tomography (CT)-guided FNA showed groups of spindle cells having elongated nuclei, fine to moderately coarsely granular chromatin, inconspicuous nucleoli, and delicate cytoplasm. Marked nuclear atypia, mitotic figures, and necrosis were absent. The differential diagnosis included a variety of benign and malignant spindle cell neoplasms such as monophasic synovial sarcoma, leiomyoma, peripheral nerve sheath tumor, fibrosarcoma, and, less likely, metastatic melanoma and sarcomatoid carcinoma. The bland-appearing cytologic features of a spindle cell tumor in a patient with osteomalacia should suggest the diagnosis of PMT.

Apocrine adenosis is a distinctive breast lesion, which can sometimes be misdiagnosed as malignant histologically. Although its histological characteristics have been well established, there are limited descriptions of its cytological features. We report fine-needle aspiration (FNA) cytology of three cases of apocrine adenosis. There were diverse cytological features between cases, and in two cases, FNA smears were highly cellular. Naked nuclei were present in all cases, and were numerous in one. Enlarged nucleoli and anisonucleosis were common. Apocrine metaplasia with nuclear atypia mimicking apocrine carcinoma was prominent in one case, whereas one case lacked definite apocrine features. Regardless of their various atypical FNA cytologies, the nuclei were consistently less hyperchromatic in all cases. Although FNA cytology of apocrine adenosis has the potential to be misinterpreted as malignant, the naked nuclei of background and less hyperchromatic nuclear features may be useful in distinguishing apocrine adenosis from carcinoma. Being familiar with these distinctive breast lesions is also important in decreasing false positives.

The diagnosis of mucinous pancreatic lesions, which include mucinous noncystic adenocarcinoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and mucinous metaplasia, is critical, given different clinical management and prognosis. This retrospective study is done to assess the cytological features and pitfalls associated with these entities in cytological samples. A search for pancreatic cytology specimens with histological confirmation of the various pancreatic mucinous lesions was done from 1988 to 2005: 9 mucinous adenocarcinoma, 14 IPMN, 11 MCN, and 3 mucinous metaplasia. The majority (35/37) had been endoscopic ultrasound-guided fine-needle aspirations. The cellularity, background extracellular mucin, epithelial architecture, mucinous nature of the epithelium, cell shape, and nuclear features were evaluated on the cytology material. Of the 22 cytological features evaluated, the presence of three-dimensional clusters, micropapillary structures, and nuclear atypia, which includes nuclear crowding, increased N/C ratio, anisonucleosis, nuclear membrane contour irregularity, clumpy chromatin, and prominent nucleoli, was found to be consistently associated with mucinous adenocarcinoma. There were no statistically significant cytological features, which helped in differentiating IPMN, MCN, and mucinous metaplasia. There was a relatively high false-positive rate in the IPMN group (5/14, 36%). Review of the histological specimen showed severe dysplastic epithelial change in these cases. One false-positive case of mucinous metaplasia (1/3, 33%) showed marked intraepithelial acute inflammation. The cytological diagnosis of mucinous pancreatic lesions remains challenging, except for mucinous noncystic adenocarcinoma. The findings were largely nonspecific in the differentiation between IPMN, MCN, mucinous metaplasia, and incidentally sampled gastrointestinal epithelium. False-positive diagnosis of adenocarcinoma occurs not infrequently in the setting of IPMN with severe dysplastic epithelial change and in lesions with associated acute inflammation, and can be a pitfall in the diagnosis of these lesions. Diagn. Cytopathol. 2006;34: 724–730. © 2006 Wiley-Liss, Inc.

Papillary neoplasms of breast constitute a group of lesions that show broad spectrum of morphological changes, ranging from benign to malignant and posing challenges at all diagnostic levels. Some benign papillary lesions may form well-defined solid masses with a dominant sclerosed architecture, known as complex sclerosing papillary lesion or simply sclerosing papilloma. The purpose of this study is to apply the previously published criteria for papillary lesions and to identify the cytomorphologic findings that lead to false-positive diagnosis of these cases. We reviewed the fine needle aspiration biopsies (FNAB) of six histologically proven sclerosing papilloma that were called suspicious or malignant on FNAB. The patient age ranged from 40 to 69, with a mean of (43 +/- 6) yr. Three patients presented with a palpable lump and two patients had history of fibrocystic disease. All six patients had abnormal screening mammograms. FNAB was performed using a 23-gauge syringe attached to a commercial holder. FNA smears were markedly hypercellular with large number of epithelial fragments and papillary clusters, discohesive single cells that are hyperchromatic with mild to moderate nuclear pleomorphism. Bipolar cells were present in all cases, varying from low to abundant. Intraoperative consultation was requested on four cases. Touch preparations were made on two cases and were reported as suspicious based on the cellularity and nuclear atypia. All surgically excised specimens showed sclerosing complex papillary proliferative lesions with epithelial hyperplasia. In conclusion, FNA cytology of this proliferative lesions may be highly cellular and may display cellular atypia similar to breast carcinoma and thus leads to false-positive interpretation.

Fine-needle aspiration cytolotogy (FNAC) is an acknowledged method for diagnosing prostate cancer. False-positive results are uncommon, but concerns have been raised that prostatic intraepithelial neoplasia (PIN) could be misinterpreted as carcinoma. Therefore, we attempted to describe cytological features of PIN. Cells were scraped from macroscopically normal areas of 177 radical prostatectomy specimens, smeared and Giemsa-stained. Histological slides from these areas were reviewed, and 17 samples with high-grade PIN and with no invasive cancer were selected. Smears from 17 invasive cancers were used for comparison. Cancer showed high cellularity and dissociation, while PIN smears only contained a few clusters of atypical cells. Pronounced nuclear atypia, prominent or multiple nucleoli and mucin were more common in cancer, while cytoplasmic granules, crystalloids and cluster size did not distinguish between PIN and cancer. In conclusion, PIN should not be diagnosed by FNAC alone. However, a highly cellular smear with pronounced atypia seems to preclude PIN. Diagn. Cytopathol. 2006;34:317–322. © 2006 Wiley-Liss, Inc.

We report a case of adenomyoma of the uterus that was cytologically difficult to distinguish from leiomyosarcoma. Examination of a uterine cervical smear revealed numerous spindle cells that were present in cell clusters or as isolated cells. These cells contained nuclei that were oval-shaped/elongated with nucleoli and delicate wispy cytoplasm. Large and bizarre nuclei were also identified. Based on these cytological findings leiomyosarcoma was considered: however, this diagnosis remained uncertain because of the absence of mitosis and/or necrotic substance. Histologically, we recognized leiomyomatous smooth muscle cells growing in a solid pattern and intermingled with endometrial-type glands. Moreover, bizarre smooth muscle cells were observed in the surface layer of the tumor. These observations suggest that for a diagnosis of uterine leiomyosarcoma the presence of mitosis and/or necrosis is important in addition to nuclear atypia.

This study was undertaken to determine the discriminating cytological features between nonhigh-grade duct carcinoma in situ (NHGDCIS) and benign breast lesions and to determine any histological characteristics which would influence the cytological categorization. Smears of 12 each of histologically confirmed NHGDCIS and benign breast lesions were reviewed with regard to cellularity, cell discohesion, nuclear atypia, crowding of cells, tubule formation, necrosis, and presence of bare atypical nuclei and regular bare bipolar nuclei, and statistically analyzed. Architectural pattern, presence of necrosis, and the size of the lesion assessed at histological examination were compared with the initial cytological categorization. NHGDCIS lesions showed more cell discohesion (P = 0.04), bare atypical nuclei (P = 0.05), necrosis (P = 0.03), and sparse bare bipolar nuclei (P = 0.02) than benign lesions. These differences were statistically significant. Cellularity (P = 0.8), nuclear atypia (P = 0.06), crowding of cells (P = 0.1), and tubule formation did not show a significant difference. Six (out of six lesions) with a solid architectural pattern and six (of seven) with necrosis could be cytologically categorized as suspicious or malignant. Size of the lesion did not influence this. We conclude that cell discohesion, bare atypical and bare bipolar nuclei, and necrosis are discriminating features between NHGDCIS and benign breast lesions and NHGDCIS lesions with a solid architectural pattern and necrosis are more likely to be satisfactorily categorized cytologically. Diagn. Cytopathol. 2004;30:98–102. © 2004 Wiley-Liss, Inc.