Imprint cytologic features of pulmonary large cell neuroendocrine carcinoma: Comparison with classic large cell carcinoma

The World Health Organization (WHO) categorized large cell neuroendocrine carcinoma (LCNEC) as a variant of large cell carcinoma in 1999. However, cytologic features of these tumors have not yet been adequately characterized. The cytologic features of 24 cases of LCNEC were analyzed and compared to the features of 16 cases of classic large cell carcinoma (CLCC). Giant cells, neutrophils and cytophagocytosis were observed more frequently in CLCC than in LCNEC (p<0.05), whereas the unclear border of tumor cells was seen more frequently in LCNEC (p<0.05). The presence of nuclear atypia, such as anisokaryosis, nuclear budding, irregularity of nuclear margins, and multinucleation (having three or more nuclei), was observed less frequently in LCNEC. Characteristic arrangements of tumor cells, such as rosette formation, and palisading, were observed only in LCNEC cases. In morphometric studies, the nuclear areas, cytoplasmic areas, and nuclear rotundity ratios were significantly higher in CLCC cells than in LCNEC cells (p<0.05). However, N/C ratios were significantly higher in LCNEC than in CLCC. LCNEC cells have less nuclear atypia than CLCC cells, and have the characteristic arrangements of tumor cells, such as palisading and rosette. It is possible to preoperatively differentiate LCNEC from CLCC by careful cytologic characterization.     

Small-sized adenocarcinoma of the lung. Cytologic characteristics and clinical behavior

BACKGROUND: Although the cytologic characteristics of advanced adenocarcinomas of the lung have been described, the unique cytologic features of early adenocarcinomas have not been established. METHODS: Cytologic specimens from 193 patients with small-sized lung adenocarcinoma, up to 2 cm in dimension, were reviewed. Cytologic investigations were performed on sputum, bronchial brushings or washings, or fine-needle aspirates obtained from the patients preoperatively. The cytologic characteristics of early adenocarcinoma were confirmed with Image Processor for Analytical Pathology from Sumitomo Chemical Co., Ltd. RESULTS: Nuclear size, variations in nuclear size, appearance of nucleolus, and nuclear atypia of the adenocarcinoma cells were found to differ between the various histologic subtypes of adenocarcinoma. The nuclei in small but advanced adenocarcinoma were generally larger and showed more variation in size than those in early adenocarcinoma (localized bronchioloalveolar carcinoma). CONCLUSIONS: Surgically curable, early adenocarcinomas of the lung were found to have a unique cytologic appearance, including small nuclear size and slight variation in nuclear size. Using these unique characteristics, they can be distinguished easily from advanced adenocarcinomas.     

肺硬化性血管瘤临床病理分析

 目的 探讨肺硬化性血管瘤（SHL）的临床病理特点。方法 对11例肺硬化性血管瘤进行光镜和免疫组化观察并结合文献进行分析。结果 SHL主要由圆形细胞和表面立方细胞二种细胞类型组成。组织结构多样，主要表现为实性区、乳头区、血管瘤样区和硬化区等四种结构。免疫组化标记二种细胞共同表达TTF-1和EMA。 结论 SHL为起源于原始的呼吸道上皮细胞的肿瘤，实性的圆形细胞和表面的立方细胞均为肿瘤细胞。形态应与炎性假瘤、肺Ⅱ型细胞乳头状瘤、肺泡腺瘤、典型类癌鉴别。部分SHL有侵袭性生长的倾向，外科手术治疗宜行肺叶切除术而非肿块剥离术。     

Fine-needle aspiration cytology of mucinous tumors of the pancreas

BACKGROUND: Tumors of the pancreas associated with extracellular mucin production include mucin-producing ductal adenocarcinoma, mucinous cystic neoplasm (MCN), and intraductal papillary mucinous tumor (IPMT). Fine-needle aspiration (FNA) is used as an adjunct to radiologic analysis for the preoperative categorization of these tumors. The current study was designed to identify distinctive cytomorphologic features that would be useful for the categorization of mucinous tumors of the pancreas. METHODS: The authors evaluated Papanicolaou smears and Diff-Quik-stained smears of specimens obtained by computed tomography-guided and endoscopic ultrasound-guided FNA of the pancreas in 51 cases of mucinous tumors. In the 19 cases in which the patients underwent surgical excision after FNA, the cytologic features were compared with the histopathologic findings. The remaining cases were categorized as one of the three above-mentioned types of mucinous tumors on the basis of cytomorphologic features identified as indicative of subtype among the cases in which a cytologic-histologic correlation was performed. RESULTS: Among the 19 cases with cytologic-histologic correlation, 2 cases of serous cystadenoma and 2 cases of gastrointestinal duplication cyst were misdiagnosed on cytologic analysis as low-grade MCN. Among the remaining 15 cases, cytologic features by histologic diagnosis were as follows: ductal adenocarcinoma (n = 4): moderate to high cellularity, mild to moderate background mucin, three-dimensional clusters, high nuclear cytoplasmic ratios, and mild to moderate nuclear membrane irregularities; low-grade MCN (n = 5): mild to moderate cellularity, abundant background mucin, small clusters, and flat sheets of relatively bland glandular cells; mucinous cystadenocarcinoma (n = 1): similar to ductal adenocarcinoma but more abundant background mucin; and IPMT (n = 5): moderate to high cellularity, abundant background mucin, and prominent papillary arrangement of tall columnar cells with mild to moderate nuclear atypia. The remaining 32 cases were categorized based on cytology alone as adenocarcinoma with mucin production (n = 24) and low-grade MCN (n = 8). CONCLUSIONS: IPMT and low-grade MCN possess distinctive cytologic features that can be used to diagnose them correctly and distinguish them from one another and from other cystic tumors. Duplication cysts closely mimic low-grade MCN, which can lead to false-positive diagnoses. Because of substantial overlap in cytologic features, mucin-producing ductal adenocarcinoma was unable to be distinguished from mucinous cystadenocarcinoma cytologically.     

Pulmonary sclerosing hemangioma of the lung. A type II pneumocytoma by immunohistochemical and immunoelectron microscopic studies

Three cases of pulmonary sclerosing hemangioma were studied by immunohistochemical and immunoelectron microscopic methods using a panel of antibodies. Six cases of adenocarcinoma of the lung, three cases of normal mesothelium, and three cases of mesothelioma were used as controls. The cytoplasm of some of the sclerosing hemangioma tumor cells was positive for the anti-lung surfactant apoprotein monoclonal antibody (PE-10). These cells were the pale cells of the solid areas, the cells covering the papillary projections, and the cells lining the cleft-like spaces. These cells also were positive for conventional epithelial cell markers. Some cells also were positive for vimentin. Electron microscopic study showed that the predominant cell was a poorly differentiated pneumocyte. Immunoelectron microscopic study also demonstrated that PE-10 existed in the rough endoplasmic reticulum of some of the cells in the solid areas, in the same way as normal type II pneumocytes. We concluded that the sclerosing hemangioma is an epithelial tumor with differentiation towards type II pneumocytes.     

Diagnostic findings of bronchial brush cytology for pulmonary large cell neuroendocrine carcinomas: comparison with poorly differentiated adenocarcinomas,squamous cell carcinomas,and small cell carcinomas

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung has been proposed as a new disease entity. To establish diagnostic features, bronchial brush cytologic findings were evaluated. METHODS: Bronchial brush cytology material of 20 LCNECs was evaluated by light microscopy and stained immunocytochemically with protein gene product 9.5 (PGP9.5), neuron-specific enolase, and neural cell adhesion molecule antibodies. The findings were compared with those for 19 poorly differentiated adenocarcinomas (ACs), 18 poorly differentiated squamous cell carcinomas (SCCs), and 20 small cell lung carcinomas (SCLCs). RESULTS: Frequently observed characteristic cytologic findings of LCNECs were necrotic background (90.0%), large tumor cell size (90.0%), naked nuclei (90.0%), and nuclear streaking (90.0%). Nuclei in all LCNECs showed a fine granular chromatin pattern and possessed one or a few nucleoli. Indian-filing and rosette arrangements were observed in less than one-half of the LCNECs. In poorly differentiated ACs and SCCs, these features were less frequent, whereas thick nuclear membranes were observed more often. In SCLCs, tumor cell adhesions and Indian-filing or nuclear molding were observed more frequently than in LCNECs, whereas a necrotic background, tumor cell clusters, large tumor cells, and nucleoli were less prominent. The majority of LCNECs (80.0%) had a positive immunocytochemical reaction for PGP9.5, in contrast to the low positive reactions for ACs (42.1%) and SCCs (30.8%). CONCLUSIONS: Large cell neuroendocrine carcinomas can be diagnosed preoperatively by bronchial brush cytology using reliable parameters, including tumor cell size, naked nuclei, thin nuclear membranes, nuclear streaking, high PGP9.5 positivity, and a necrotic background.     

Sclerosing hemangioma of the lung. Immunohistochemical characterization of its origin as related to surfactant apoprotein

Lung tissues from 13 patients with pulmonary sclerosing hemangioma were studied with antibody against surfactant apoprotein, Factor VIII-related antigen, or lysozyme. Surfactant apoprotein was detected in the cytoplasm of the cells lining cystic spaces and papillary projections. Surfactant apoprotein was found in a small number of stromal cells with abundant eosinophilic or clear cytoplasm and round to oval nuclei, which were characteristic in pulmonary sclerosing hemangioma as the main component. Surfactant apoprotein was also found in the stromal cells with small, dark nuclei similar to the lining cells. The lining and stromal cells contained neither Factor VIII-related antigen nor lysozyme. Our demonstration of surfactant apoprotein in these cells provides further support for the idea that pulmonary sclerosing hemangioma primarily consists of epithelial cells with differentiation to type II pneumocytes, as was deduced from ultrastructural investigations.     

Fine-needle aspiration of epithelioid sarcoma: cytology findings in nine cases

BACKGROUND: Epithelioid sarcoma is a rare tumor with characteristic morphologic and immunohistochemical features. It can be confused histologically and cytologically with a variety of benign and malignant lesions, including a granulomatous process, synovial sarcoma, melanoma, squamous cell carcinoma, and adenocarcinoma. The objective of this study was to define the cytologic features of this rare tumor. METHODS: The cytologic features of nine histologically confirmed epithelioid sarcomas were analyzed. The criteria evaluated included cell size and shape, cell borders, cluster organization, cytoplasmic characteristics, nuclear and nucleolar features, and background characteristics. RESULTS: In most cases, single, dispersed cells represented the predominant pattern, with only a few small clusters present. The cells were mostly round with interspersed spindle cells and mild to moderate pleomorphism. The nuclei were large and eccentrically located, with a plasmacytoid appearance. A pale zone in the perinuclear area was evident in three of nine cases. Well-defined cell borders with intercellular spaces between malignant cells were observed in eight cases. In three cases, a granuloma-like structure was identified. In two cases, the cells were mostly spindle and showed greater cellular pleomorphism. CONCLUSION: Epithelioid sarcoma is an uncommon tumor with a wide range of differential diagnoses, especially in cytology specimens. Awareness of its existence and knowledge of its cytologic features are important for a correct diagnosis.     

Cystic pancreatic endocrine tumor: a variant commonly confused with cystic adenocarcinoma

BACKGROUND: Most cystic pancreatic neoplasms are currently evaluated by an endoscopic ultrasound-guided fine-needle aspiration biopsy (FNAB). In the authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently causes diagnostic difficulties, partly because of unexpected overlapping features with cystic ductal adenocarcinomas. METHODS: The authors identified 5 histologically confirmed cystic PETs that were evaluated by FNAB and compared their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid PETs (n = 39) of the pancreas. RESULTS: Cytologically, 2 of the aspirates of cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular and composed of cohesive aggregates of monomorphic cellular elements with variably coarse chromatin. Tumor necrosis and nuclear membrane irregularities were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear membrane irregularities, and tumor necrosis. CONCLUSIONS: Given the clinical implications, awareness of cystic PETs and their deceptive cytologic features would assist in distinguishing these lesions from cystic ductal adenocarcinomas.     

High incidence of nuclear accumulation of p53 protein in gastric cancer.

The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.     

A molecular diagnostic test for distinguishing lung adenocarcinoma from malignant mesothelioma using cells collected from pleural effusions.

PURPOSE: Patients with malignant mesothelioma or adenocarcinoma of the lung often present with respiratory complications associated with a malignant pleural effusion. Distinguishing between these malignancies is frequently problematic, as many of the clinical, cytologic, and histologic features of the diseases overlap. Following cytologic analysis of pleural effusions, subsequent confirmatory tissue biopsies involve increased patient morbidity and expense. We have therefore designed a gene expression-based test to classify the primary tumor causing a malignant pleural effusion, using cells collected from the effusion itself. EXPERIMENTAL DESIGN: We have used microarray data for 190 lung adenocarcinomas and 33 malignant mesotheliomas to identify genes differentially expressed between the two diseases. Genes expressed in normal mesothelial cells were removed, allowing the development of a PCR-based test to measure the expression of genes that discriminate between mesothelioma and lung adenocarcinoma from cytology specimens. RESULTS: Applying an real-time PCR-based assay involving 17 genes to 13 independent samples from biopsy-proven malignant mesothelioma and lung adenocarcinomas resulted in the correct identification of all samples. CONCLUSIONS: We have developed a test that is able to distinguish between lung adenocarcinoma and mesothelioma in cells collected from pleural effusions.     

硬化性肺泡细胞瘤术中冰冻误诊分析及文献回顾

目的:分析硬化性肺泡细胞瘤术中冰冻切片形态特征，总结其误诊原因和鉴别要点。方法:收集2011年1月至2017年12月硬化性肺泡细胞瘤术中冰冻误诊病例4例，光学显微镜下观察冰冻切片形态特点并与术后石蜡切片对照。结果:硬化性肺泡细胞瘤冰冻切片以乳头区、实性区为主者，形态结构与细胞特点易于误诊为腺癌，血管瘤样区域易于与血管源性肿瘤混淆。结论:硬化性肺泡细胞瘤是术中冰冻误诊率较高的肿瘤，乳头样区域和实性区域尤应与乳头状腺癌和实性腺癌鉴别，结合影像学及临床特点综合分析、多处取材并应用术中细胞印片是避免误诊的有效手段。     

The cytomorphology of papillary serous carcinoma of the endometrium in cervical smears

BACKGROUND: An investigation into the determination of cytomorphologic criteria that may distinguish papillary serous carcinoma of the endometrium (PSC) from typical endometrioid carcinoma (TEC) in cervical smears was undertaken. Preoperative identification of this poor prognostic variant of endometrial carcinoma may influence the surgical management of these cases and the choice of adjuvant therapy. METHODS: The cervical smears of 12 cases of histologically confirmed PSC; 12 cases of TEC, including 2 villoglandular/papillary variants, and 6 cases of mixed PSC and papillary endometrioid carcinoma were reviewed. In all cases an initial diagnosis of malignancy had been made on the cervical smears. Twenty-seven criteria were evaluated and the relation between the cytologic characteristics and the type of adenocarcinoma, the degree of association, and the intergroup homogeneity were tested. RESULTS: Features strongly associated with PSC were hypercellular smears with a background tumor diathesis, papillae, bare nuclei, and cells with large pleomorphic nuclei and bulky dense cytoplasm. In contrast, TEC showed a relatively monomorphic population of cells with moderately enlarged oval nuclei and delicate cytoplasm. In the mixed tumors, the features were similar to those of PSC, suggesting preferential exfoliation of the PSC component of the tumor. CONCLUSIONS: Assessment of the cytomorphology of PSC and TEC of the endometrium in Papanicolaou stained cervical smears is possible using statistically significant diagnostic criteria.     

Cytopathologic factors can predict invasion in small-sized peripheral lung adenocarcinoma with a bronchioloalveolar carcinoma component

BACKGROUND: Patients with noninvasive, small-sized primary adenocarcinomas of the lung have excellent prognosis after lobectomy. Several researchers have suggested that limited resection could be an acceptable alternative for these patients. Therefore, a preoperative or intraoperative judgment of invasiveness would be one of the critical determinants of the surgical procedure in each case. Cytopathologic findings that can distinguish invasive from noninvasive adenocarcinomas remain to be elucidated. METHODS: Imprint smears were obtained from 60 resected adenocarcinomas with nonmucinous bronchioloalveolar features. Thirteen cytologic factors were evaluated: the presence of necrosis, fibrovascular tissue, proportion of macrophages, the presence of large tumor cell clusters, nuclear grooves, nuclear overlapping, variation in nuclear size, chromatin pattern, presence of a nucleolus, intranuclear inclusions, multinucleated cells, spindle cells, and mitosis. Each factor was examined by univariate analysis for correlation with the presence of histopathologic invasion. RESULTS: In the univariate analysis, 5 cytologic factors--presence of tumor cell clusters consisting of more than 50 tumor cells (P < .001), nuclear overlapping in more than 3 layers (P < .001), presence of nuclear grooves (P = .007), more than 3-fold variation in nuclear size (P < .001), and 1 mitotic cell per 1000 tumor cells (P = .035)--were associated significantly with invasion. Among these, nuclear overlapping in more than 3 layers (P = .003) and more than 3-fold variation in nuclear size (P = .005) were found to be independent predictive factors for invasion by multivariate analysis. CONCLUSIONS: Using imprint smears, the presence of invasion in small-sized primary adenocarcinomas of the lung is predictable by the 2 above-mentioned cytologic findings. Imprint smear cytology may effectively aid intraoperative judgement of invasion in cases where frozen section histology is difficult to interpret.     

A Case of Pneumocytoma (So-Called Sclerosing Hemangioma) With Lymph Node Metastasis

A case of "sclerosing hemangionia" (pneumocytoma) of the lungwith lymph node metastasis is reported. A 22-year-old Japaneseman was found to have a well-defined round lesion in the rightlung (S⁷), which increased in size slightly during a 2-yearfollow-up period. He underwent right lower lobectomy with a preoperative diagnosisof a benign lung tumor. The pulmonary tumor revealed histologicalfeatures characteristic of "sclerosing hemangioma" of the lung,in addition to which there were many large polygonal foamy cells,forming tubular or papillary structures. These cells were foundby electron microscopy to contain numerous cytoplasmic lamellarbodies and showed a positive reaction with anti-surfactant apoproteinantibody immunohistochemically. Therefore, they were consideredto be cells differentiating toward type II pneumocytes. Reviewof 21 typical "sclerosing hemangionia" disclosed a few or somesuch foamy cells in 10 cases. A single hilar lymph node wasthe site of microscopic metastases, which consisted of "largeclear foamy cells" and smaller polygonal or round cells withslightly eosinophilic cytoplasm, both of which were componentsof the pulmonary "sclerosing hemangioma" This case supportsthe theory that "sclerosing hemangioma" is a neoplasm of typeII pneumocyte lineage. Although it is said to be benign, rarecases apparently show metastatic potential.     

Mammary lesions diagnosed as "papillary" by aspiration biopsy: 70 cases with follow-up

BACKGROUND: The authors reviewed smears from fine-needle aspiration biopsies (FNAB) diagnosed as "papillary lesions" and correlated the cytologic findings with the final diagnoses at excision. The objective of the current study was to determine the accuracy of FNAB diagnosis of a papillary lesion in distinguishing true papillary from nonpapillary proliferations and to evaluate cytologic criteria for the distinction of papillomas from true papillary malignancies and their cytologic look-alikes. METHODS: The cytopathology database at the New York University Medical Center was searched for women who underwent surgical excision after a breast FNAB diagnosis of a papillary lesion. The FNAB smears and corresponding slides from excisional biopsies were reviewed. The smears were evaluated and graded for the following features: cellularity, architecture, presence of fibrovascular cores, single cells, columnar cells, cellular atypia, myoepithelial cells, foamy histiocytes, and apocrine cells. The F test was used to determine the statistical significance of differences between true benign papillary lesions (papilloma) and adenocarcinomas (in situ and invasive). RESULTS: At the time of excision, 46 (66 %) cases were benign (23 solitary intraductal papillomas, 6 intraductal papillomatosis, 11 examples of fibrocystic change, and 6 fibroadenomas) and 24 (34 %) were malignant (1 low-grade phyllodes tumor [PT], 23 ductal in situ and invasive carcinomas). Of the 23 carcinomas, 3 (13 %) were classified as benign papillary lesions on FNAB and 19 (86 %) were classified as either atypical or suspicious. One case of low- grade PT originally was classified as benign on FNAB. There were four false-negative diagnoses; two were due to sampling and two to interpretative errors. A portion of the lesions classified as papillary were fibroadenomas and examples of fibrocystic change on excision and all of these were correctly classified as benign on FNAB. Of the histologically proven papillomas, 62% were correctly classified as benign on FNAB and none were designated as being positive for malignancy. Statistically significant features of distinction between papillomas and carcinomas included cellularity (P = 0.016), cellular atypia (P = 0.0053), and the presence of cytologically bland columnar cells (P = 0.04). Low-grade ductal carcinoma in situ (cribriform and micropapillary types) and tubular carcinoma represented the most difficult differential diagnostic problems. CONCLUSIONS: A significant portion of lesions displaying a papillary pattern on FNAB are nonpapillary on follow-up. Among benign processes, fibrocystic change and fibroadenoma may closely simulate papilloma on cytology. However, in spite of the overlapping features of true papillary lesions and their cytologic look-alikes, the majority can be classified accurately into benign or atypical (and above) categories by FNAB. Lesions that fall short of a definitive benign diagnosis should be placed into an indeterminate category. This approach will guide the surgeon to provide better patient management.     

Cystic pancreatic endocrine tumor

BACKGROUND.

Most cystic pancreatic neoplasms are currently evaluated by an endoscopic ultrasound‐guided fine‐needle aspiration biopsy (FNAB). In the authors' experience, FNAB of cystic pancreatic endocrine tumors (PETs) frequently causes diagnostic difficulties, partly because of unexpected overlapping features with cystic ductal adenocarcinomas.

METHODS.

The authors identified 5 histologically confirmed cystic PETs that were evaluated by FNAB and compared their cytomorphologic features to cystic ductal adenocarcinomas (n = 5) and solid PETs (n = 39) of the pancreas.

RESULTS.

Cytologically, 2 of the aspirates of cystic PETs were devoid of tumor cells whereas the other 3 were variably cellular and composed of cohesive aggregates of monomorphic cellular elements with variably coarse chromatin. Tumor necrosis and nuclear membrane irregularities were not identified in cystic PETs. Alternatively, in contrast to PETs, cystic ductal adenocarcinomas were characterized by nuclear pleomorphism, nuclear membrane irregularities, and tumor necrosis.

CONCLUSIONS.

Given the clinical implications, awareness of cystic PETs and their deceptive cytologic features would assist in distinguishing these lesions from cystic ductal adenocarcinomas. Cancer (Cancer Cytopathol) 2007 © 2006 American Cancer Society.     

Cytomorphologic features of papillary lesions of the male breast: a study of 11 cases

BACKGROUND: Breast masses occur in men far less commonly than women and are infrequently subjected to fine-needle aspiration (FNA) biopsy. Papillary lesions of the male breast are rare and are comprised of a spectrum of lesions ranging from papillary hyperplasia in gynecomastia to invasive papillary carcinoma. The following study describes the cytomorphology of papillary breast lesions in 11 men. The patients ranged in age from 23 to 78 years old and each presented with an unilateral subareolar or periareolar breast mass that varied in size from 0.5 to 3 cm. Two patients presented with bloody nipple discharge. METHODS: Archival material (8-year period) from FNA biopsies of papillary lesions of the male breast was reviewed. The reviewed cases were correlated with appropriate clinicopathologic follow-up. RESULTS: The smears had variable cellularity but all showed papillary clusters of mammary epithelial cells with and without fibrovascular cores. Single epithelial cells with a high nuclear-to-cytoplasmic ratio and eccentric nuclei were seen in all smears; however, these were more numerous in cases of adenocarcinoma. Hemosiderin-laden macrophages were present in all cases. Nipple discharge was seen only in the 2 benign lesions. All adenocarcinomas occurred in older men. CONCLUSIONS: The only cytologic criteria that differentiated benign from malignant papillary lesions were marked cellularity and the presence of abundant 3-dimensional clusters. To the best of the authors' knowledge, the current series is the largest in the English literature to date that examines the cytomorphologic features of papillary breast lesions in men.     

The cytologic basis for classification of lung tumors

Nuclear changes in cells of bronchial biopsies and surgical specimens were studied in relation to nuclear structures of cells at various mitotic phases. Cell structures comparable to early and late G1 and G2 phases were correlated with histologic types of lung tumors according to the 1981 WHO classification. The evolved cellular classification added another parameter for diagnosis of histologic alterations and for interpretation of cellular changes in cytologic specimens. Benign histological alterations contained cells in either early or late G1 phase. Well-differentiated adenocarcinomas, bronchiolo-alveolar cell carcinomas, and carcinoid tumors had cells with structure of the late G1 phase. These were distinguished from benign cells with similar structures by their increased nuclear size, their increased amount of nuclear chromatin, hyperchromasia, and increased nuclear cytoplasmic ratio. Well-differentiated acinar adenocarcinomas, papillary adenocarcinomas, clear cell carcinomas, and large cell carcinomas had cribriform nuclear structures with prominent nucleoli related to early G2 phase. Squamous cell carcinomas, poorly differentiated adenocarcinomas, giant cell carcinomas, and solid carcinomas with mucus formation had usually prominent nucleoli with nuclear structures of the late G2 phase. Small cell carcinomas were the only malignant tumors of the lung that had cells with the malignant cribriform nuclear structure of the early G2 phase without a nucleolus. Cellular markers of malignant neoplasms had also the nuclear structure of early G2 without a nucleolus but differed from small cell carcinoma by their differentiated state with presence of cilia. The cytologic diagnosis of 506 malignant tumors of 1031 cases examined resulted in a sensitivity of 86.6%. The correct diagnosis of 244 of 247 cases without tumor resulted in a diagnostic specificity of 98.8%.     

"Histiocytoid" cells in fine-needle aspirations of papillary carcinoma of the thyroid: frequency and significance of an under-recognized cytologic pattern

BACKGROUND: Although the classic cytologic features of papillary carcinoma of the thyroid in fine-needle aspirates have been well described, one uncommon feature, a vacuolated, histocyte-like cell without classic nuclear changes of papillary carcinoma, has been less well characterized. METHODS: The author reviewed a large series of thyroid aspirates for specimens with these cytologic features. RESULTS: Seven specimens were identified, representing approximately 6% of all aspirates with the features of papillary carcinoma and less than 0.5% of all aspirates. The cells resembled histiocytes but were larger, more atypical, and keratin positive in the one specimen that was tested. The cells had enlarged nuclei with abundant cytoplasm that often was vacuolated. The nuclei had grainy chromatin, occasional nucleoli, and lacked grooves and prominent pseudoinclusions. The background showed numerous, hemosiderin-laden macrophages typical of cyst contents in only three specimens. Calcifications were present in six specimens and resembled psammoma bodies in two specimens. Three specimens showed papillary carcinoma at resection, two specimens had other passes from the same nodule that were diagnostic of papillary carcinoma, and two specimens were from recent patients without follow-up. Only one of the three resected tumors showed prominent cystic change. None of 50 aspirates that were diagnosed as benign cyst contents had similar atypical cells, nor did resections of six predominantly cystic, benign lesions. CONCLUSIONS: Histiocytoid cells are present in as many as 6% of all aspirates in which some features of papillary carcinoma are present. Increased awareness of these cells may help improve the sensitivity of fine-needle aspiration for the diagnosis of papillary carcinoma of the thyroid.