Cytological cell blocks: Predictors of squamous cell carcinoma and adenocarcinoma subtypes.

Fine needle aspirations biopsies, CT-guided and endobronchial ultrasound-guided, as a mode of diagnosing and/or staging lung carcinoma, are becoming more frequent. Also, there is greater necessity for classification of lung cancers into subcategories of squamous cell carcinoma and adenocarcinoma for appropriate management. Cytomorphology, based on smears alone, allows this classification in many instances. The aim of the current study was to explore the potential of cell blocks to increase the specificity of diagnosis. The morphological characteristics of sixty-two lung carcinomas were examined. Less well-differentiated squamous cell carcinomas were more readily classified as such on cell blocks. Likewise, cell block sections with architectural patterns including strips of cells, papillae and nests of cells correlated with bronchioalveolar, papillary and acinar/mixed subtypes of adenocarcinoma on follow-up histology. In conclusion, cell blocks provide additional morphological clues and material for ancillary studies for classification of lung carcinomas.

Variation in vascular distribution in small lung cancers.

PURPOSE: To assess the vascular component of small lung cancers. MATERIAL AND METHODS: We identified 105 resected non-small-cell lung carcinomas without pathologic evidence of vascular, lymphatic, bronchial, or pleural invasion. The percentage of BAC (% BAC) of all adenocarcinomas was determined by a pulmonary pathologist. A representative histology slide of each carcinoma was digitally scanned and the number of blood vessels (#V) with at least a diameter of 200microm was identified as well as the area of these blood vessels (VA) and of the tumor (TA) was obtained. The CT consistency of the cancers was also recorded as non-solid (NS), part-solid (PS) and solid. RESULTS: The number of blood vessels per cm(2) of tumor area (#V/TA) was higher for adenocarcinoma (7.3+/-4.7) as compared with large- and squamous-cell carcinoma (3.6+/-2.1, 2.3+/-1.1, respectively, P<0.0001). For adenocarcinoma, #V/TA decreased with decreasing % BAC from 10.3 vessels per cm(2) of tumor area for 100% BAC to 5.1 vessels per cm(2) of tumor area for 0% BAC. The ratio of the total vascular area to tumor area (VA/TA), however, did not differ significantly by cell type nor for the adenocarcinoma by % BAC (P=0.87). While #V/TA decreased from 9.6 for non-solid nodules, to 7.5 for part-solid nodules and to 5.1 for solid nodules, there was no significant difference (P=0.27) in the VA/TA ratio by nodule consistency. Overall, VA comprised 2.7% of the total tumor area (TA) for 105 cancers. CONCLUSIONS: These results suggest that tumor vessels experience a continuous temporal and spatial remodeling as tumors grow and that bigger tumors tend to have fewer but larger blood vessels. It also suggests that, on average, squamous- or large-cell carcinomas have a larger average vessel diameter as compared with adenocarcinomas and that the vasculature of an adenocarcinoma might remodel as the % BAC decreases. The overall proportion of tumor volume comprised of vessels 200microm or larger is small and unlikely to influence overall tumor volume and doubling time estimates.

CXCL12 and CXCR4 in adenocarcinoma of the lung: association with metastasis and survival.

OBJECTIVES: Although the chemokine CXCL12 and its receptor CXCR4 have been implicated in metastasis of non-small cell lung carcinoma, the prognostic significance of these molecules is poorly defined. This study aimed to determine whether expression of these molecules is associated with clinicopathologic features and disease-free survival in non-small cell lung carcinoma. METHODS: Immunohistochemical staining for CXCL12 and CXCR4 was performed on 154 primary non-small cell lung carcinomas. Staining intensity was compared with tumor histotype, TNM stage, and disease-free survival; correlation was assessed by using the Fisher's exact test, and Kaplan-Meier and Cox multivariate proportional hazards regression analysis. RESULTS: Intense CXCL12 immunostaining was associated with nodal metastasis, although no difference in survival was observed. The prognostic relevance of CXCR4 was dependent on its subcellular location: in univariate analysis intense nuclear staining was significantly associated with lower T classification and improved disease-free survival in patients with adenocarcinoma, whereas cytomembranous staining was associated with distant metastasis and decreased disease-free survival. On multivariate analysis, cytomembranous CXCR4 expression conferred a significantly worse disease-free survival (relative risk, 2.8; 95% confidence interval, 1.4-5.7; P = .004). CONCLUSIONS: Cytomembranous expression of the chemokine receptor CXCR4 in adenocarcinoma of the lung is an independent risk factor associated with worse disease-free survival, whereas nuclear staining confers a survival benefit. These findings are consistent with a model in which CXCR4 promotes tumor cell proliferation and metastasis when present in the cytoplasm or cell membrane, whereas localization of this molecule in the nucleus prevents it from exerting these effects.

Papillary thyroid carcinoma with atypical histiocytoid cells on fine-needle aspiration.

Although papillary thyroid carcinoma (PTC) usually has classic cytological characteristics on fine-needle aspiration (FNA), it can present rarely with aberrant features resembling those of histiocytes in a cystic nodule. The aim of the current study was to describe PTC with atypical histiocytoid cells and distinguish it from benign histiocytes. A retrospective computerized search for FNAs with atypical features suggestive of PTC and cystic degeneration was performed, and if available, the corresponding resection specimens were compared. Four cases met the criteria for FNAs and three had surgical pathology follow-up, which showed PTC. One aspirate had some features typical of PTC, but the remaining FNAs had atypical histiocytoid cells, which had traits intermediate between those of PTC and histiocytes. Large cell size, pseudoinclusions, nuclear grooves, and multiple well-defined vacuoles in atypical histiocytoid cells favor PTC over benign histiocytes. Ancillary immunocytochemical studies can also be useful in confirming the diagnosis. Histiocytic cells are frequently present in thyroid aspirates, and occasionally, they have atypical features that represent an unusual presentation of PTC. Closer examination of these cells can provide diagnostic clues for preventing false-negative diagnosis of PTC.

Fine-needle aspiration biopsy of a papillary thyroid carcinoma involved by malignant plasma cell disease: a case report.

We described the fine-needle aspiration biopsy findings in a case of papillary thyroid carcinoma involved by a malignant plasma cell disease of the thyroid gland in a 54-year-old female. Although papillary thyroid carcinoma is the most common malignant tumor of the thyroid gland, involvement by plasma cell disease is exceptionally unusual.

Immunohistochemical expression of estrogen and progesterone receptors in primary pulmonary neuroendocrine tumors.

CONTEXT: Lung and breast carcinomas are among the most prevalent cancers. Advances in cancer therapies can provide survival benefit and be potentially curative, even in metastatic disease. Due to the high prevalence of these carcinomas, it is not unusual to encounter lung nodule(s) in a patient with breast carcinoma, and distinguishing between primary and metastatic disease is critical for management/treatment. Occasionally neuroendocrine differentiation is present in breast carcinoma, making its distinction from pulmonary/nonpulmonary neuroendocrine tumors in the lung difficult. OBJECTIVE: To assess estrogen and progesterone receptor expression in the entire spectrum of pulmonary neuroendocrine tumors. DESIGN: Seventy-one neuroendocrine neoplasms including typical carcinoids (42), atypical carcinoids (7), small cell carcinomas (14), large cell neuroendocrine carcinomas (2), and combined small cell carcinomas (6) were evaluated for estrogen and progesterone receptors. Mammary and non-small cell lung carcinomas were also stained for comparison. RESULTS: The entire spectrum of neuroendocrine neoplasms demonstrated focal to diffuse estrogen (typical carcinoid, 23; atypical carcinoid, 6; small cell carcinoma, 8; large cell neuroendocrine carcinoma, 2; combined small cell carcinoma, 4) and progesterone (typical carcinoid, 11; atypical carcinoid, 2; small cell carcinoma, 7; large cell neuroendocrine carcinoma, 0; combined small cell carcinoma, 2) expression. There was no correlation between sex and estrogen/progesterone status. Estrogen and progesterone staining were also noted in endothelial cells. Relative to neuroendocrine carcinomas, mammary carcinomas expressed estrogen and progesterone more frequently. Non-small cell carcinomas had greater and similar immunoreactivity for estrogen and progesterone, respectively. CONCLUSIONS: Although estrogen and progesterone receptor staining is frequently associated with breast and gynecologic primaries, it can also be observed in "nontarget" organs. Therefore, presence of estrogen and/or progesterone expression in neuroendocrine tumors involving the lung should not exclude a primary pulmonary neoplasm.

The use of genetic markers to identify lung cancer in fine needle aspiration samples.

PURPOSE: We seek to establish a genetic test to identify lung cancer using cells obtained through computed tomography-guided fine needle aspiration (FNA). EXPERIMENTAL DESIGN: We selected regions of frequent copy number gains in chromosomes 1q32, 3q26, 5p15, and 8q24 in non-small cell lung cancer and tested their ability to determine the neoplastic state of cells obtained by FNA using fluorescent in situ hybridization. Two sets of samples were included. The pilot set included six paraffin-embedded, noncancerous lung tissues and 33 formalin-fixed FNA specimens. These 39 samples were used to establish the optimal fixation and single scoring criteria for the samples. The test set included 40 FNA samples. The results of the genetic test were compared with the cytology, pathology, and clinical follow-up for each case to assess the sensitivity and specificity of the genetic test. RESULTS: Nontumor lung tissues had < or= 4 signals per nucleus for all tested markers, whereas tumor samples had > or = 5 signals per nucleus in five or more cells for at least one marker. Among the 40 testing cases, 36 of 40 (90%) FNA samples were analyzable. Genetic analysis identified 15 cases as tumor and 21 cases as nontumor. Clinical and pathologic diagnoses confirmed the genetic test in 15 of 16 lung cancer cases regardless of tumor subtype, stage, or size and in 20 of 20 cases diagnosed as benign lung diseases. CONCLUSIONS: A set of only four genetic markers can distinguish the neoplastic state of lung lesion using small samples obtained through computed tomography-guided FNA.

Cell block alone as an ideal preparatory method for hemorrhagic thyroid nodule aspirates procured without onsite cytologists.

OBJECTIVE: To study diagnostic efficacy of direct smears (DS) vs. cell block (CB) alone in hemorrhagic thyroid fine needle aspirations (FNAs) performed without a cytotechnologist or cytopathologist. STUDY DESIGN: Ultrasound-guided thyroid FNAs from an offsite location were retrospectively searched during a 53-month period. Aspirates in the initial 13 months were submitted as air-dried DSs. Subsequent specimens were submitted as CBs. Each case was classified into 1 of 4 categories: (1) nondiagnostic, (2) nonneoplastic, (3) follicular lesions and (4) papillary thyroid carcinoma (PTC). RESULTS: There were 77 aspirates: DS = 20 (26%) and CB = 57 (74%). Two cases had both DSs and CBs. Diagnoses of DS: nondiagnostic = 12 (60%); nonneoplastic = 7 (35%); follicular lesion = 1 (5%). Diagnoses of CB cases: nondiagnostic = 4 (7.0%); nonneoplastic = 43 (75.4%); follicular lesion, including 1 Hürthle cell neoplasm = 7 (12.3%), PTC = 3 (5.3%). Repeat FNAs on 4 nondiagnostic cases (3 DSs, 1 CB) utilizing the CB-only technique were diagnostic and included nodular goiter, follicular neoplasm, PTC, and reactive lymph node. CONCLUSION: Without onsite assessment, CB alone is superior to DSs for hemorrhagic thyroid FNAs. It shows increased diagnostic efficacy and slide reduction and obviates repeat FNAs.

PAX-5 expression in pulmonary neuroendocrine neoplasms: its usefulness in surgical and fine-needle aspiration biopsy specimens.

The World Health Organization classification of lung tumors recognizes 4 histologic subtypes of pulmonary neuroendocrine carcinomas (NECs), which include typical carcinoids (TCs), atypical carcinoids (ACs), small cell carcinomas (SCCs), and large cell NECs (LCNECs). These tumors can be misclassified owing to morphologic parallels, indicating the necessity for adjunctive tests for correct classification. We evaluated immunohistochemical expression of PAX-5 in histologic and fine-needle aspiration (FNA) specimens of pulmonary NECs. Staining was stratified by intensity (0 to 3+) and percentage of cells stained as focal (<10%) or diffuse (=10%). PAX-5 expression was present in 29/37 (78%) of high-grade NECs (22/26 SCCs, 1/2 LCNECs, and 6/9 combined tumors) and none of 51 TCs and ACs; FNA specimens showed concordant staining. This study confirmed that PAX-5 is a useful marker in FNA and surgical specimens for the discrimination of low- to intermediate-grade NECs from high-grade NECs with 100% specificity and 79% sensitivity in surgical specimens.

Reliability of cytologic diagnosis of early lung cancer.

BACKGROUND: Baseline screening for lung cancer of 2968 high-risk men and women utilizing HRCT enrolled in ELCAP (Early Lung Cancer Action Project) was performed between 1993-2002. Among them, 65 people had surgical resection of their screen-diagnosed lung cancer, 53 of them on the basis of a diagnosis of malignancy or atypical bronchioloalveolar proliferation (ABP) on fine needle aspiration (FNA) biopsy at Weill Medical College of Cornell University (WMC) prior to surgery. The authors compared the diagnosis obtained from the FNA with the subsequent diagnosis from the surgical specimen to assess the reliability of a cytologic diagnosis of lung cancer on FNA of these screen-diagnosed lung cancers. METHODS: The FNA biopsies were performed with a 22-gauge Wescott needle by 1 radiologist (D.Y.), with preliminary on-site as well as final diagnosis rendered by a cytologist (M.V., J.K.). These results were correlated with histologic diagnoses obtained as a result of consensus diagnosis by a panel of 5 expert pulmonary pathologists. RESULTS: Of the 53 cases of lung cancer resected following FNA, 4 were diagnosed as atypical bronchioloalveolar proliferation (ABP), 14 as adenocarcinoma with bronchioloalveolar features (ADC-BAC), 28 as adenocarcinoma, not otherwise specified (ADC-NOS), 1 as squamous cell carcinoma (SQCC), 4 as nonsmall-cell carcinoma (NSCC), and 2 as typical carcinoid. In the 49 cases with a malignant cytology and 4 cases of ABP, lung cancer was confirmed histologically. The tumor sizes ranged from 4 mm to 40 mm, mean size 13mm. The final expert panel histologic diagnosis was adenocarcinoma in 47 cases; of these, 42 were invasive (mixed subtype or acinar subtype), and 5 were a noninvasive (bronchioloalveolar carcinoma, BAC). Three of the 42 invasive adenocarcinoma that had a predominant BAC component and 1 case of BAC were diagnosed as ABP on FNA; all were sampled at the periphery of the tumor. Three of 4 cases of invasive adenocarcinoma of high nuclear grade were diagnosed as NSCC, and 1 was inaccurately classified as SQCC on FNA. One case of high-grade noninvasive BAC associated with a scar was diagnosed as NSCC on FNA. Two cases classified as nonkeratinizing SQCC and 2 cases of large cell neuroendocrine carcinoma on histology were misclassified as ADC-NOS by FNA. Two cases of typical carcinoid on histology were also diagnosed as typical carcinoid on FNA. CONCLUSIONS: Preoperative diagnosis of lung cancer detected by screening with HRCT could be reliably made by FNA. Difficulty in classification occurs in carcinomas of high nuclear grade with prominent nucleoli, including poorly differentiated SQCC and large cell neuroendocrine carcinoma. These are best diagnosed as NSCC on cytomorphology with further subclassification based on immunohistochemistry, which these authors generally perform on cell-block material. A diagnosis of ABP on FNA may be indicative of noninvasive BAC or an invasive adenocarcinoma with prominent BAC features, usually sampled at its periphery.

Endoscopic ultrasound-guided biopsies of pancreatic masses: comparison between fine needle aspirations and needle core biopsies.

Endoscopic ultrasound-guided fine needle aspiration (EUS-guided FNA) is a highly sensitive and specific method for diagnosing pancreatic masses. Alternatively, EUS-guided needle core biopsies (NCB) have also been introduced. We sought to determine efficacies of pancreatic EUS-guided FNAs and NCBs. Records of consecutive EUS-guided FNAs received over a 24-mo-period were reviewed. Cases with concurrent NCBs were selected for the study. The diagnoses from the two modalities were compared and designated concordant (CC) or discordant (DC). Of 252 cases, 52 had concurrent NCBs. The final diagnoses included primary and secondary tumors. Of the 52 cases, 29/52 (55.8%) were CC and 23/52 (44.2%) were DC. The sensitivities for FNAs and NCBs were 95.0% and 67.6%, respectively. Both modalities were 100% specific. Direct comparison between EUS-guided FNAs and NCBs demonstrated that the former are more sensitive for diagnosing pancreatic neoplasms, both primaries and metastases. There was no correlation between CC/DC cases and type of neoplasm.

Clear cell and eosinophilic oncocytomas of salivary gland: cytological variants or parallels?

Oncocytomas are uncommon tumors of the salivary gland. They have an abundance of mitochondria, which is manifested as granular eosinophilic cytoplasm by light microscopy. On histological sections, presence of cytoplasmic glycogen and/or fixation artifact can impart cytoplasmic clearing, and oncocytomas with a predominance of clear cytoplasm are labeled clear cell oncocytomas. Two forms of oncocytoma, eosinophilic and clear cell, have been described in the surgical pathology literature. The purpose of this manuscript is to conduct a comparative cytological assessment to ascertain parallels and differences between the two variants.

Bronchioloalveolar carcinoma in small pulmonary nodules: clinical relevance.

Increased use of chest computed tomography (CT) as well as improvements in CT resolution has led to increased detection of subcentimeter pulmonary nodules. Although the majority of these nodules are benign in etiology, a subset will harbor bronchioloalveolar carcinoma. The diagnosis of malignancy in this setting can be challenging to radiologists, surgeons, and occasionally pathologists as well. The challenge is compounded by a lack of knowledge about the natural course of these lesions--specifically, whether they represent life-threatening aggressive malignancies or indolent lesions of little or no consequence. Given the relative infrequency of these abnormalities, it will be essential to establish a sufficiently large database, to organize multi-institutional registries, and to collaborate on correlative studies. Only in this way will we be able to determine the clinical and molecular characteristics of these lesions and thus hopefully gain insight into their clinical relevance.

Metastatic mammary carcinomas with endocrine features: potential diagnostic pitfalls.

Mammary carcinomas with endocrine differentiation (MCED) are an uncommon subtype of breast carcinomas that are morphologically indistinguishable from low-grade endocrine neoplasms arising in other organs. Aspirates of MCED yield relatively monotonous cells with eccentrically placed nuclei containing characteristic "salt and pepper" chromatin. In the breast, these features represent MCED. In extramammary sites, the differential is more extensive, and diagnosing MCED metastases to the lung, a common location for primary and metastatic endocrine tumors, can be a challenging task, with significant clinical implications. Although primary MCED have been described extensively in the cytology literature, secondary pulmonary MCED have not been reported to the best of our knowledge. We report three cases of MCED metastatic to the lung and present the cytological and immunohistochemical features.