Cytodiagnosis of hepatocellular carcinoma in fine-needle aspirates of the liver: its differentiation from reactive hepatocytes and metastatic adenocarcinoma

Fine-needle aspiration (FNA) cytology is a useful tool for diagnosis of primary malignancies and metastatic lesions of the liver. However, well-differentiated hepatocellular carcinoma (HCC) may resemble benign/reactive hepatocytes, and less differentiated HCC may simulate poorly differentiated adenocarcinoma, leading to difficulties in interpretation of aspirates from liver. To determine the subtle cytomorphological features which can differentiate these lesions, ultrasound-guided FNA smears from 86 cases of liver malignancy were subjected to detailed cytologic assessment. These included 20 cases of HCC, 38 cases of metastatic adenocarcinoma, and 28 cases of benign/reactive hepatocytes. The important features for separating HCC or well-differentiated HCC from benign/reactive hepatocytes were excessive cellularity, trabecular pattern vs. thin cords of hepatocytes, nuclear pleomorphism, atypical stripped nuclei, and macronucleoli (P < 0.001 to < 0.0001). The most significant features for differentiating HCC from metastatic adenocarcinoma were trabecular growth pattern, hepatocytic cells vs. columnar/cuboidal cells, eosinophilic granular cytoplasm, lipid vacuoles, bile pigments, and atypical stripped nuclei (P < 0.001 to < 0.0001). The cytomorphological features which may distinguish poorly differentiated HCC from poorly differentiated adenocarcinoma were polygonal (hepatocytic) cells, eosinophilic granular cytoplasm and lipid vacuoles in HCC, and columnar/cuboidal cells and acinar/glandular formation in adenocarcinoma (P < 0.05 to < 0.001). Diagn. Cytopathol. 1999;21:370-377.     

An approach to fine-needle aspiration biopsy diagnosis of hepatic masses

After reviewing collection techniques and the cytology of normal and reactive hepatocytes, a systematic approach to the evaluation of fine-needle aspiration biopsy smears of hepatic mass lesions is presented. One of the main problems facing the cytopathologist is the differentiation of cirrhosis from well-differentiated hepatocellular carcinoma. Smears from patients with cirrhosis often contain clusters of bile duct epithelial cells and chronic inflammatory cells, while properly sampled hepatocellular carcinoma smears should contain no bile duct epithelial cells and few inflammatory cells. Key criteria which favor the diagnosis of hepatocellular carcinoma over cirrhosis are: increased nuclear to cytoplasmic ratio, trabecular pattern, and atypical naked hepatocytic nuclei. Key criteria which favor the diagnosis of primary hepatocellular carcinoma over metastatic disease include polygonal cells with centrally placed nuclei, cells separated by sinusoidal capillaries, and bile. This systematic approach to the evaluation of hepatic fine-needle aspiration biopsies must be used with the realization that other uncommon mass lesions of the liver do exist (focal nodular hyperplasia, adenoma, hepatoblastoma, bile duct carcinoma, vascular tumors, mesenchymal tumors, and lymphomas).     

Endoscopic bile duct brushing of malignant pancreatic biliary strictures: retrospective study with comparison of conventional smear and ThinPrep techniques

Endoscopic bile duct brushing (EBDB) is carried out to differentiate benign from malignant biliary strictures in patients who have pancreaticobiliary disease. The sensitivity of this method for the diagnosis of malignancy is relatively low. The aim of this study is to analyze the cytomorphologic features that are helpful in increasing the sensitivity of detecting these lesions on cytologic samples. These features are compared with slides prepared with the ThinPrep technique. The study included 142 patients with bile duct obstruction or pancreatic mass who underwent EBDB and follow-up surgery or biopsy between 1997 to 2000. Twenty-five (18%) of these cases were positive for malignancy in both EBDB and follow-up surgical biopsy; 20 of these cases were used as positive controls (PC). Sixty-one (43%) were negative in both EBDB and follow-up surgical biopsy specimens, and 21 of those cases were used as negative controls (NC). Fifty-six (39%) cases were negative/atypical in EBDB cytology but were suspicious or positive in the surgical or biopsy specimens (false-negative). We identified the cytologic criteria that were helpful in differentiating our positive and negative control groups and applied these criteria to our false-negative group to see whether our sensitivity could be increased, using well-defined cytologic criteria alone. Of the 56 false-negative cases, 9 (16%) were upgraded to suspicious/positive based on the presence of the following features: three-dimensional (3D) micropapillae (95% PC vs 19% NC, P < 0.0001), anisonucleosis (90% PC vs 5% NC, P < 0.0001), high nuclear-to-cytoplasmic (N/C) ratio (95% PC vs 9% NC, P < 0.0001), nuclear contour irregularity (65% PC vs 24% NC, P = 0.0079), and prominent nucleoli (70% PC vs 38% NC, P = 0.0406). Cytomorphologic features which were not helpful in distinguishing positive and negative cases were: single naked nuclei (50% PC vs 28% NC, P = 0.1597), chromatin granularity (50% PC vs 62% NC, P = 0.54), and necrosis (10% PC vs 5% NC, P = 0.5197). Improvement in diagnostic sensitivity for carcinoma of pancreaticobiliary tract in EBDB samples may be achieved by identifying the key malignant cytomorphologic features: 3D micropapillae, anisonucleosis, nuclear contour irregularity, prominent nucleoli, and high N/C ratio. The sensitivity in detecting malignant biliary strictures increased from 31% to 42% based on these criteria in our current study.     

Fibroadenomas with atypia: causes of under- and overdiagnosis by aspiration biopsy.

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine-needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false-negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under- or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false-positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern.     

Pancreatic adenocarcinoma: regression analysis to identify improved cytologic criteria

The incidence of pancreatic adenocarcinoma is increasing and it is usually unresectable at the time of diagnosis. Consequently, fine-needle aspiration biopsy (FNAB) is being used more frequently for diagnosis. The reported sensitivity of diagnosing pancreatic adenocarcinoma by FNAB has varied between 50% and 100%. In an attempt to increase the diagnostic sensitivity, we retrospectively reviewed a series of pancreatic FNABs. Fifteen cytologic criteria were evaluated in 78 patients who had pancreatic FNABs. Of these patients, 49 had primary adenocarcinomas and 29 had benign, non-neoplastic lesions. Using a stepwise logistic regression analysis we identified three key cytologic criteria for this diagnosis. Our study identified anisonucleosis (P = 0.001), large nuclei (P = .007), and nuclear molding (P = .03) as the significant cytologic features for diagnosing pancreatic adenocarcinoma. In combination, these three criteria had a sensitivity of 98% and a specificity of 100%.     

Fine-needle aspiration biopsy of breast adenomyoepithelioma: A potential false positive pitfall and presence of intranuclear cytoplasmic inclusions

Cytologic diagnosis of adenomyoepithelioma can be very challenging. We report fine needle aspiration cytology (FNAC) findings of a benign adenomyoepithelioma. The cytologic features are characterized by hypercellularity and the presence of numerous atypical dispersed cells with epithelioid morphology and intact cytoplasm. The nuclei showed stippled chromatin, irregular nuclear membrane, and prominent eosinophilic nucleoli. No necrosis or mitoses were seen. The presence of naked nuclei, and extensive intranuclear cytoplasmic inclusions were identified and raised the possibility of adenomyoepithelioma. Immunohistochemically, the atypical cells showed strong positivity for myosin heavy chain, p63, and CK5/6, while the epithelial cells reacted with estrogen receptors. This immunophenotypic pattern supports the myoepithelial origin of the atypical cell proliferation and favors the diagnosis of benign adenomyoepithelioma. However, biopsy was recommended to exclude malignancy. Histologically, the tumor showed prominent myoepithelial cells with significant atypia, intranuclear cytoplasmic inclusions, and dense cytoplasm. No evidence of malignancy was identified. In conclusion, we report a case of adenomyoepithelioma with a significant cytological atypia that may result in confusion with malignant breast tumors. The presence of intranuclear cytoplasmic inclusions, naked nuclei, and expression of myoepithelial markers should provide clues to the right diagnosis and benign nature of this lesion. Cytopathologists should be familiarized with this entity to avoid a misdiagnosis of carcinoma. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.     

Histiocytic aggregates in benign nodular goiters mimicking cytologic features of papillary thyroid carcinoma (PTC)

Macrophages/histiocytes are commonly seen in fine-needle aspiration biopsy (FNAB) specimens of thyroid nodules with varying degrees of cystic change. In some cases the histiocytic component of a cystic thyroid nodule can occur as large tissue fragments with marked nuclear atypia, including elongated nuclei with chromatin clearing, nuclear grooves, and membrane thickening. These nuclear changes mimic cytologic features of papillary thyroid carcinoma (PTC), thus leading to diagnostic difficulty in interpretation of FNAB specimens of benign cystic thyroid nodules. We evaluated ethanol-fixed Papanicolaou-stained smears of 273 cases of FNAB thyroid specimens from goitrous nodules with cystic change. Twenty cases were selected due to the presence of large aggregates of histiocytic cells with the above-mentioned nuclear atypia. An immunostain for histiocytic cells using CD68 was performed on alcohol-fixed slides. Histiocytic cells in tissue fragments with nuclear atypia mimicking PTC nuclei showed strong cytoplasmic staining for CD68; thyroid follicular cells stained negative for CD68. We conclude that histiocytic cells in cystic goitrous nodules can show nuclear features, which appear similar to PTC nuclei. Immunostaining for CD68 may be of value in differentiating between benign cystic thyroid nodules with histiocytic aggregates that mimic cytologic features of papillary carcinoma, and PTC with cystic change.     

Endocervical adenocarcinoma in situ: An analysis of cellular features

Cytologists increasingly encounter atypical endocervical cells, because of the increasing incidence of endocervical adenocarcinoma and the use of improved endocervical sampling devices. These atypical endocervical cells can cause diagnostic problems, especially in recognizing adenocarcinoma in situ (AIS) and distinguishing it from a variety of nonneoplastic changes. We analyzed 33 cervical smears from 22 patients with confirmed AIS and compared these to 19 cervical smears from 17 patients having atypical endocervical cells of undetermined significance and negative follow-up, including at least one tissue biopsy per case, to further investigate the cytologic features of AIS. The AIS smears typically had crowded three-dimensional cellular aggregates, with markedly hyperchromatic nuclei having altered polarity. Frequently, a minor component of AIS formed strips of distinctly columnar cells or sheets. Individual AIS cells occurred in 22 (67%) smears, but these were usually inconspicuous. The AIS smears also had increased nuclear to cytoplasmic ratios (100%), enlarged nuclei (94%), feathering (88%), rosettes (85%), nucleoli (76%), apoptosis (73%), mitoses (64%), multiple nucleoli (18%), and ciliated atypical cells (3%). Cytologic features occurring significantly (P ≤ 0.001) more often in AIS cases were a predominance of three-dimensional crowded aggregates (79% vs. 32%), altered nuclear polarity in most groups (88% vs. 16%), marked hyperchromasia (91% vs. 16%), apoptosis (73% vs. 26%), an increased nuclear to cytoplasmic ratio (100% vs. 63%), feathering (88% vs. 26%), and individual atypical cells (67% vs. 16%). In summary, we identified a number of architectural and cellular features that occurred significantly more often in AIS cases than in cases having atypical endocervical cells of undetermined significance and negative follow-up. Diagn. Cytopathol. 1997;17:326–332. © 1997 Wiley-Liss, Inc.     

Low-grade urothelial carcinoma: reappraisal of the cytologic criteria on ThinPrep

The diagnostic criteria for low-grade urothelial lesions that have been described in the past were based on urinary specimens prepared by the cytospin method. Recognizing the recent popularity of the ThinPrep methodology and the cytologic alterations it introduces to the cellular features, we sought to evaluate the reproducibility of these criteria in ThinPrep urinary samples. One hundred twenty-six ThinPrep urinary specimens with a tissue diagnosis of low-grade urothelial carcinoma (LGUC) and 45 negative controls were evaluated. Three pathologists blindly reviewed the slides separately and the consensus on each feature was used in the study. Logistic regression analysis was used to determine which criteria in combination were most predictive of low-grade urothelial carcinoma. All specimens were evaluated for the following 18 features: nucleus/cytoplasm ratio, irregular nuclear border, cytoplasm homogeneity, cell clusters, high cellularity, prominent nucleoli, granular nuclear chromatin, hyperchromasia, acute inflammation, vesicular chromatin, nuclear molding, nuclear eccentricity, elongated nuclei, necrosis, anisonucleosis, irregular bordered fragments, absent cytoplasmic collar, and peripheral palisading. High nucleus-to-cytoplasm ratio, irregular nuclear borders, and homogeneous cytoplasm (combination sensitivity of 59% and specificity of 100%) were the best predictive features for LGUC. Minor predictive criteria were eccentric nuclei and nuclear molding. ThinPrep provides well preserved, cleaner specimens without significantly altering the morphology. The three key criteria applied in cytospin specimens to diagnose LGUC were reproducible in ThinPrep specimens.     

Comparative features of comedo and noncomedo ductal carcinoma in situ of the breast on fine-needle aspiration biopsy.

To determine whether fine-needle aspiration biopsy (FNAB) can differentiate between comedo (C-DCIS) and noncomedo ductal carcinoma in situ (NC-DCIS), we reviewed retrospectively the preoperative FNAB and surgical biopsy slides of 13 cases of DCIS with adequate cytologic material. Eight were NC-DCIS and 5 were C-DCIS. Three (60 percent) of the C-DCIS and 7 (88%) of the NC-DCIS were nonpalpable lesions biopsied under conventional mammographic guidance. Three (60%) of the C-DCIS but only 2 (25%) of the NC-DCIS were considered either suspicious or positive for malignancy on FNAB, the remainder in both groups being atypical. A statistically significant difference in marked nuclear pleomorphism (60% of C-DCIS vs. 0% of NC-DCIS, P = 0.04) and large nucleoli (60% of C-DCIS vs. 0% of NC-DCIS, P = 0.04) was observed between these 2 groups. DCIS is morphologically diverse, and it appears that the cytologic features of individual cells on FNAB may distinguish C-DCIS from NC-DCIS.     

Epithelial cell atypia in bronchoalveolar lavage specimens from lung transplant recipients.

In lung transplant recipients, bronchoalveolar lavage (BAL) is mainly performed to detect infectious agents. However, in addition to microorganisms, epithelial cell atypia may be identified, and determination of its significance is necessary. Specimens obtained at BAL in lung and heart-lung transplant recipients (LTRs) between 1991 and 1998 were examined for the presence of significant cytologic atypia in epithelial cells. Ten cases in 9 patients were identified, and these composed the core of our study. These transplant BAL specimens were compared with 4 BAL specimens with carcinoma from non-transplant patients (NTPs). Fourteen cytologic parameters were evaluated, and clinical and biopsy correlation was made in each case. Significant overlap in cytologic features, including background cellularity, number of atypical cell clusters, number of cells in each cluster, size of cell clusters, contour of clusters, 3-dimensionality, tenacious intercytoplasmic connections, multinucleation, nuclear size, nuclear/cytoplasmic ratio, nuclear membrane irregularity, chromatin pattern, intranuclear inclusions, and nucleolar characteristics, was observed between atypical LTR cases and NTP carcinoma cases. Clinically, all LTR cases derived from nonneoplastic conditions including harvest injury (diffuse alveolar damage), acute cellular rejection, and infections. Our study results show that evaluation of cytologic features alone does not permit differentiation of atypical cells found in nonneoplastic conditions from those in malignant conditions. Clinical and histologic correlation and awareness of the range of atypia seen in posttransplant syndromes is important in correct interpretation of these cases.     

Cytopathologic differential diagnosis of small cell carcinoma and poorly differentiated non‐small cell carcinoma in bronchial lavage specimens using a regression analysis

Cakir E, Demirag F, Aydin M. Cytopathologic differential diagnosis of small cell carcinoma and poorly differentiated non‐small cell carcinoma in bronchial lavage specimens using a regression analysis. APMIS 2010; 118: 150–55. The aim of this study was to determine the most significant cytologic features to differentiate small cell carcinoma (SCC) from poorly differentiated non‐small cell carcinoma (NSCC) in bronchial lavage specimens. Bronchial lavage specimens from 35 SCC cases and 63 poorly differentiated NSCC cases were examined and the cytologic parameters reviewed retrospectively. Thirty‐five cytologic features considered useful in differential diagnosis were assessed. Statistical analysis indicated that salt and pepper chromatin, small cell size and nuclear molding have more than 90% sensitivity and 70% specificity for SCC cases. Logistic regression analysis demonstrated that the most effective criteria to differentiate SCC from poorly differentiated NSCC are small cell size, salt and pepper chromatin, prominent nucleolus and papilla formation. When these selected variables were used, sensitivity for predicting SCC was 94.3% and specificity 96.8%, and sensitivity for predicting NSCC was 96.8% and specificity 94.3%. There are several cytologic features, which are highly sensitive and specific for distinguishing SCC from NSCC. Nuclear features such as chromatin pattern, and size of the nucleoli and nuclei are more valuable than cytoplasmic features to distinguish between the two.     

Successful grading of renal-cell carcinoma in fine-needle aspirates

Early-stage renal-cell carcinoma is more frequently diagnosed due to more frequent use of advanced radiologic techniques. Partial nephrectomy may be curative for small tumors and may sometimes be necessary if the opposite kidney is functionally compromised. This therapeutic option is however not possible in high-grade neoplasms. In the current study, we attempted to grade cases of renal-cell carcinoma on smears obtained from preoperative fine-needle aspirates (FNA). Eighteen cases of histologically proven renal-cell carcinoma formed the basis of this study. FNAs were performed prior to nephrectomy. FNA smears were blindly reviewed, and the cases were evaluated for cellularity, nuclear to cytoplasmic (N/C) ratios, nuclear pleomorphism, and the presence of naked nuclei and prominent nucleoli; cases were graded according to the presence or absence of these criteria and their combination. The cases were cytologically graded from grade I-IV and then were given a low grade if the tumor was considered grade I or II, or high grade if the tumor was considered grade III or IV. The histology of the neoplasms was reviewed, and the tumors were graded according to the Fuhrman nuclear grading system. Correlation between the cytologic and histologic grades within the same histologic grade was seen in 13 of the 18 cases (72.2%). The difference was no more than one grade for each discrepancy. When grading as high or low grade was used, agreement was seen in 100% of the cases. The most reliable cytologic features seen on cytology distinguishing low- from high-grade tumors were the N/C ratio and the presence or absence of nucleoli. Pleomorphism, naked nuclei, and increased cellularity were less distinguishing features. We conclude that grading of renal-cell carcinoma can be reliably achieved in FNA material. Preoperative FNAs can thus be performed on small renal neoplasms with subsequent conservative treatment if the tumor proves to be low grade.     

Atypical cells in bronchoalveolar lavage specimens from bone marrow transplant recipients. A potential pitfall

Numerous nonneoplastic conditions of the lungs may result in atypical cells in bronchoalveolar lavage (BAL) specimens mimicking malignant neoplasms. Bone marrow transplant (BMT) recipients have many predisposing factors that would lead to atypical cells in BAL specimens, presenting diagnostic challenges. We reviewed BAL specimens from BMT recipients and correlated our findings with clinical information. During a 5.5-year period, 21 BMT recipients had atypical cells in 27 BAL specimens at Fairview-University Medical Center, Minneapolis, MN. The atypical cells had the cytologic features of squamous or glandular cells. The nuclear/cytoplasmic ratio, atypical cells per case, and background varied from case to case. Most of the patients had 1 or more of the clinical findings that would lead to atypia in BAL specimens: 13 had recent cytoreductive treatment, 9 had positive cultures, and 7 had graft-vs-host disease. There was substantial overlap between the reactive atypia and carcinoma. Clinical correlation was the most important factor in making accurate diagnosis.     

Cytologic criteria used to diagnose adenocarcinoma in pleural effusions.

A stepwise logistic regression analysis was employed to evaluate the usefulness of the following criteria to distinguish adenocarcinoma in pleural effusion from benign pleural effusion: increased size of nucleus, increased nuclear to cytoplasmic ratio, irregular nuclear borders, sharply defined cytoplasmic boundaries, large nucleoli, aggregates with variable size nuclei, aggregates with nuclear overlap, irregular noncentral vacuoles, aggregates with nuclear molding, multinucleation, three-dimensional aggregates, aggregates with large cytoplasmic vacuoles, atypical mitoses, nuclear vacuoles, homogeneous cytoplasm, aggregates with associated lymphocytes and neutrophils, and uniform size aggregates. A total of 223 patients with benign pleural effusion cases and 221 patients with adenocarcinoma in their pleural effusion were scored as to the presence or absence of the above criteria. The resulting data were subjected to a stepwise logistic regression analysis that chose increased nuclear/cytoplasmic ratio, irregular nuclear borders, large nucleoli, sharply defined cytoplasmic boundaries, and three-dimensional aggregates as the best criteria to differentiate adenocarcinoma in pleural effusion from benign pleural effusion. When used together, these five features had a sensitivity of 94% and a specificity of 93% for predicting adenocarcinoma.     

The cytology of pancreatic foamy gland adenocarcinoma

All cell block specimens from pancreatic fine-needle aspirations (FNAs) obtained between January 1, 2002, and June 30, 2003, were reviewed for foamy gland adenocarcinoma (FGA). All smears from these cases were reviewed for cytologic features, including those previously noted in conventional pancreatic adenocarcinoma. Fifty-two cell block specimens showed adenocarcinoma. Of these, 12 (23%) showed histologic features of FGA. This pattern predominated in 6 cases and was present focally in 6 cases. Although there were relatively low nuclear/cytoplasmic (N/C) ratios, other features of adenocarcinoma were present universally, including loss of cohesiveness, nuclear overlap or loss of "honeycomb" architecture, anisonucleosis (> 4 to 1), irregular nuclear contours, prominent nucleoli, and atypical chromatin. Background necrosis was present in 8 cases. Distinct cell borders were present in 9 cases, and foamy cytoplasm was present in all cases. Pancreatic FGA is a recently described histologic pattern of pancreatic adenocarcinoma. It is not uncommon, and we identified the pattern, at least focally, in 23% of our FNA cell blocks. Although cytologic samples show low N/C ratios, most cytologic features of conventional pancreatic adenocarcinoma are present, and the diagnosis presents little additional difficulty.     

Cytologic criteria for fibroadenoma. A step-wise logistic regression analysis

The authors reviewed the fine-needle aspiration biopsy smears from 62 subjects with proven fibroadenoma, 60 subjects with proven ductal carcinoma, and 42 subjects with proven fibrocystic disease. All smears were coded as to the presence or absence of the following variables: epithelial cells, stroma, honeycomb sheets, antler horn clusters, naked nuclei, nucleoli, marked cellularity, foam cells, apocrine cells, anisokaryosis, atypical nuclear hyperchromasia, single cells with cytoplasm, mitotic figures, and nuclei greater than two red blood cell diameters. Step-wise logistic regression analyses were performed to determine the variables predictive of fibroadenoma. The statistical analyses selected stroma, antler horn clusters, and marked cellularity as the key cytologic criteria to differentiate fibroadenomas from fibrocystic disease. The statistical analyses selected stroma, antler horn clusters, and honeycomb sheets as the key cytologic criteria to differentiate fibroadenoma from ductal carcinoma.     

Cytopathologic differential diagnosis of low‐grade urothelial carcinoma and reactive urothelial proliferation in bladder washings: a logistic regression analysis

Conventional cytomorphologic assessment is the first step to establish an accurate diagnosis in urinary cytology. In cytologic preparations, the separation of low‐grade urothelial carcinoma (LGUC) from reactive urothelial proliferation (RUP) can be exceedingly difficult. The bladder washing cytologies of 32 LGUC and 29 RUP were reviewed. The cytologic slides were examined for the presence or absence of the 28 cytologic features. The cytologic criteria showing statistical significance in LGUC were increased numbers of monotonous single (non‐umbrella) cells, three‐dimensional cellular papillary clusters without fibrovascular cores, irregular bordered clusters, atypical single cells, irregular nuclear overlap, cytoplasmic homogeneity, increased N/C ratio, pleomorphism, nuclear border irregularity, nuclear eccentricity, elongated nuclei, and hyperchromasia (p ? 0.05), and the cytologic criteria showing statistical significance in RUP were inflammatory background, mixture of small and large urothelial cells, loose monolayer aggregates, and vacuolated cytoplasm (p ? 0.05). When these variables were subjected to a stepwise logistic regression analysis, four features were selected to distinguish LGUC from RUP: increased numbers of monotonous single (non‐umbrella) cells, increased nuclear cytoplasmic ratio, hyperchromasia, and presence of small and large urothelial cells (p = 0.0001). By this logistic model of the 32 cases with proven LGUC, the stepwise logistic regression analysis correctly predicted 31 (96.9%) patients with this diagnosis, and of the 29 patients with RUP, the logistic model correctly predicted 26 (89.7%) patients as having this disease. There are several cytologic features to separate LGUC from RUP. Stepwise logistic regression analysis is a valuable tool for determining the most useful cytologic criteria to distinguish these entities.     

Cytology of low-grade endocrine neoplasms involving liver: a series of 24 specimens, including 4 with hepatoid or glandular features

Low-grade endocrine neoplasms (LGENs) involving the liver usually show typical endocrine features. Occasionally these tumors display cytologic characteristics that mimic hepatocellular carcinoma (HCC) or adenocarcinoma (ACA). Twenty-four liver FNABs from 22 patients were reviewed. Twenty specimens showed cytologic characteristics typical of LGENs, including small to medium-sized cells with salt-and-pepper or granular chromatin, moderate to high N/C ratios, and inconspicuous or absent nucleoli. Plasmacytoid cells were observed in 19 cases. Immunocytochemical stains (ICCs) confirmed endocrine differentiation in 9 cases. 4 FNABs were comprised of larger tumor cells that displayed cytologic features that overlapped with HCC or ACA, including transgressing or wrapping endothelium, moderate to abundant cytoplasm, and conspicuous nucleoli. LGENs involving the liver typically demonstrate characteristic cytologic features. Cases comprised of larger cells with abundant cytoplasm, conspicuous nucleoli, and transgressing or wrapping endothelium may pose diagnostic difficulties. ICCs and plasmacytoid morphology are beneficial in classifying the endocrine origin of these tumors.     

Diagnostic utility of CD10 in differentiating hepatocellular carcinoma from metastatic carcinoma in fine-needle aspiration biopsy (FNAB) of the liver

The differential diagnosis between hepatocellular carcinoma (HCC) and metastatic carcinoma, especially in moderate-poorly differentiated (MPD) HCC and poorly differentiated carcinoma, can be challenging in fine-needle aspiration biopsy (FNAB) of the liver. Recent studies demonstrate that canalicular staining for CD10 appears to be a highly specific marker for hepatocytic differentiation. The objective of this study was to test the utility of CD10 in differentiating HCC from metastatic carcinoma in FNAB of the liver. Formalin-fixed, paraffin-embedded cell blocks of 55 cases (22 HCC, 23 metastases, and 10 benign hepatic lesions) of FNAB of the liver were immunostained using monoclonal antibody against CD10, with microwave oven antigen retrieval, followed by a standard ABC method. Nineteen (86%) of 22 HCC cases were positive for CD10 with a canalicular staining pattern. Among them, 9 (82%) of 11 well-differentiated (WD) HCC and 10 (91%) of 11 MPD HCC were positive for CD10. Three (13%) of 23 metastatic carcinomas were positive for CD10, demonstrating a contrasting cytoplasmic and membranous staining pattern. The three positive cases were metastatic renal cell carcinoma (RCC), choriocarcinoma, and adenocarcinoma of the lung. All 10 cases of benign hepatic lesions showed positivity for CD10 with a canalicular and focal membranous staining pattern. In conclusion, CD10 appears to be a useful marker in discriminating between HCC and metastatic carcinoma when applied to FNAB of the liver. CD10 does not provide discrimination between WD HCC and benign hepatocytes.