Diffusion-weighted imaging in characterization of cystic pancreatic lesions.

AIM: To evaluate whether apparent diffusion coefficient (ADC) measurements from diffusion-weighted imaging (DWI) can characterize or predict the malignant potential of cystic pancreatic lesions. MATERIALS AND METHODS: Retrospective review of the magnetic resonance imaging (MRI) database over a 2-year period revealed 136 patients with cystic pancreatic lesions. Patients with DWI studies and histological confirmation of cystic mass were included. In patients with known pancreatitis, lesions with amylase content of >1000 IU/l that resolved on subsequent scans were included as pseudocysts. ADC of cystic lesions was measured by two independent reviewers. These values were then compared to categorize these lesions as benign or malignant using conventional MRI sequences. RESULTS: Seventy lesions were analysed: adenocarcinoma (n=4), intraductal papillary mucinous neoplasm (IPMN; n=28), mucinous cystic neoplasm (MCN; n=9), serous cystadenoma (n=16), and pseudocysts (n=13). There was no difference between ADC values of malignant and non-malignant lesions (p=0.06), between mucinous and serous tumours (p=0.12), or between IPMN and MCN (p=0.42). ADC values for low-grade IPMN were significantly higher than those for high-grade or invasive IPMN (p=0.03). CONCLUSION: ADC values may be helpful in deciding the malignant potential of IPMN. However, they are not useful in differentiating malignant from benign lesions or for characterizing cystic pancreatic lesions.

A prospective study comparing rapid assessment of smears and ThinPrep for endoscopic ultrasound-guided fine-needle aspirates.

BACKGROUND AND STUDY AIMS: ThinPrep is often used for endoscopic ultrasound fine-needle aspiration (EUS-FNA) samples but the sensitivity of this method is unknown. The objective of the study was to compare sensitivity and accuracy of ThinPrep versus the smear method in pancreas and lymph node samples obtained by EUS-FNA. PATIENTS AND METHODS: Patients with suspected malignancy in the pancreas or lymph node underwent EUS-FNA. On-site rapid assessment of all aspirates using the smear method was performed. After rapid assessment, three additional passes from each site were submitted into ThinPrep liquid medium. Cytopathologists interpreting the smear method and ThinPrep slides were blinded to each other. The gold standard was final cytology or pathology results. RESULTS: A total of 130 patients (36 % women, mean age 63 years) underwent EUS-FNA of 139 sites (50 pancreas, 89 lymph node). Malignancy was confirmed in 47 pancreas samples (94 %) and 48 lymph node samples (54 %). Mean +/- SD number of passes made for the smear method was 2.6 +/- 1.3. For pancreatic cancer, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the ThinPrep versus the smear method were: 62 % versus 98 %, 100 % versus 100 %, 100 % versus 100 %, 14 % versus 75 %, and 64 % versus 98 %, respectively. For lymph nodes the values were 67 % versus 92 %, 100 % versus 98 %, 100 % versus 98 %, 72 % versus 72 %, and 82 % versus 94 %, respectively. CONCLUSIONS: The smear method is more sensitive and accurate than ThinPrep in detecting malignancy from EUS-FNA samples of the pancreas and lymph nodes. Smear method with on-site rapid assessment should be favored over ThinPrep in suspected malignancy.

Detection of multiple human papillomavirus types in the lower genital tract correlates with cervical dysplasia.

Some human papillomavirus (HPV) types, such as HPV 16, are clearly associated with cervical dysplasia; however, the role played by other HPV types occasionally found in dysplasia is less certain. In addition, most methods used to detect HPV in clinical specimens cannot easily distinguish among more than two or three HPV types in a single specimen. Therefore, the significance of infection with multiple HPV types is not known. To address this question, we analyzed cervicovaginal lavage specimens from three cohorts of women for HPV DNA using a PCR/reverse blot assay system that permits the detection and partial quantitation of 26 genital HPV types. As expected, 94.1% of women who had dysplasia (n = 34) and 71.4% of women who had atypical squamous cells of uncertain significance (ASCUS) (n = 21) on cytology had HPV DNA detected compared to 54.5% of age matched women with normal cytology. HPV 16 DNA was detected in 35% of dysplasia patients compared to 9% of cytologic normals (P = 0.0044). Dysplasia patients had a mean of 3.29 (range 0-10) different HPV types detected compared to 1.04 (range 0-7) HPV types among those with normal cytology (P < 0.0001). These data support a possible role for multiple HPV types in the development or progression of cervical dysplasia.

Fine-needle aspiration cytology of cystic hypersecretory ductal carcinoma in situ of the breast: a case report.

Cystic hypersecretory intraductal carcinoma is an unusual, cystic form of intraductal breast carcinoma affecting middle-aged women. Cytopathologists have rarely encountered this lesion, with only 2 other cases having been previously reported (Colandrea et al., Arch Pathol Lab Med 1988:112:560-563; Kim et al., Acta Cytol 1997;41:892-896). In our cases, the cytologic findings of both air-dried, Diff-Quick-stained and ethanol-fixed, Papanicolaou-stained smears are presented. The cytologic hallmarks of this entity include the presence of a few scattered epithelial cells with bland nuclear morphology in a background of extensive, amorphous, pink-staining material. Cytomorphologically, the differential diagnosis includes other entities containing pink-staining material such as colloid carcinoma, mucocele-like lesion of the breast, and benign fibrocystic change.

Fine needle aspiration cytology of benign adrenal cortical nodules. A comparison of cytologic findings with those of primary and metastatic adrenal malignancies.

OBJECTIVE: To determine the specific cytomorphologic criteria for diagnosing benign adrenal cortical nodule (BACN) by fine needle aspiration (FNA). STUDY DESIGN: The smears from 162 adrenal FNA biopsies were reviewed. A diagnosis of BACN was rendered in 50 cases (31%). The cytologic features of BACN were compared to those of primary and metastatic malignant tumors of the adrenal gland, and the size of BACN as measured by computed tomography was recorded. RESULTS: Bubbly, vacuolated, lipid background; large, cohesive tissue fragments with a syncytial nesting arrangement admixed with sinusoidal endothelial cells; and abundant oval, round, bare nuclei are the three cytomorphologic features most often seen in BACN. The combination of these three features was observed in 40 cases (89%) of BACN and was seen in 4 cases of metastatic carcinoma (6%) in which there was also coexisting adrenal cortical hyperplasia. None of the other primary or metastatic malignancies showed this combination of cytomorphologic features. The mean size of BACN was 2.5 cm, with a standard deviation of 1 cm and a range of 1-5 cm. The sizes of the four metastatic carcinomas with coexisting adrenal cortical hyperplasia were 6.5, 6, 5 and 1.5 cm, respectively (mean, 4.8). CONCLUSION: Our data suggest that combined cytologic features of bare nuclei; bubbly, vacuolated background; and large, cohesive tissue fragments with sinusoidal endothelial cells in a small adrenal nodule (< 3.5 cm) are highly specific to FNA diagnosis of BACN.

Fine-needle aspiration biopsy of metastatic Ewing's sarcoma with MIC2 (CD99) immunocytochemistry.

The use of fine-needle aspiration biopsy (FNAB) has been infrequently described as a diagnostic modality for Ewing's sarcoma (ES) patient follow-up and management. The purpose of this study is to examine the use and accuracy of FNAB combined with MIC2 immunocytochemistry for evaluating metastases in patients with ES. Records from Saint Louis University Health Sciences Center and Indiana University Medical Centers identified patients with known ES who had undergone FNAB for evaluation of potential metastases. Immunocytochemical analysis for MIC2 (CD99) was performed retrospectively on cell blocks and direct aspirate smears. FNABs from nine patients were procured either percutaneously or under radiologic guidance and in all cases a definitive cytologic diagnosis of metastatic ES was rendered. Aspirates were cellular with many single discohesive small round cells and occasional loosely cohesive clusters. The nuclei were round with a fine chromatin pattern and small nucleoli. The cytoplasm was scanty and the nuclear-cytoplasmic ratio was high. Six of six cases showed strongly positive immunocytochemical labeling for MIC2. Immunocytochemistry with MIC2 in FNAB aspirate smears can provide supportive evidence of ES in patients with known disease.

Fine needle aspiration biopsy of recurrent and metastatic osteosarcoma.

OBJECTIVE: To assess the utility of fine needle aspiration (FNA) biopsy in evaluating local recurrence or disseminated metastases in patients with osteosarcoma. STUDY DESIGN: Cytology files from Saint Louis University Hospital and Indiana University Medical Center were searched for patients with osteosarcoma who had undergone FNA biopsy for evaluation of local recurrence or disseminated metastases. Clinical information was collected and all aspirate smears reviewed. RESULTS: Six FNA biopsies in five patients were procured by either the percutaneous or radiologically guided method. All six aspirates were diagnostic. Cytologic features showed a discohesive, cellular neoplasm with intermediate to large cells and oval to spindle nuclei. Chromatin was coarsely granular, with single or multiple nucleoli. Aspirate material included multinucleated giant cells and a variable amount of "osteoidlike" extracellular matrix. CONCLUSION: FNA biopsy is accurate, and these results reflect its ability to diagnose osteosarcoma when there is local recurrence or widely disseminated metastases.

Fine needle aspiration cytology of metastatic olfactory neuroblastoma.

OBJECTIVE: Olfactory neuroblastoma (ONB) is an uncommon malignant neoplasm that originates in the upper nasal cavity. Cytomorphologic descriptions of ONB have been limited to isolated case reports. The features of a series of metastatic ONB diagnosed by fine needle aspiration (FNA) are described. STUDY DESIGN: Cytologic findings in four patients with ONB metastatic to cervical lymph nodes who underwent FNA were reviewed, and the cytomorphologic findings were summarized. Immunocytochemical findings and ultrastructural features with selected immunoelectron microscopy from three cases are described. RESULTS: Aspiration cytology revealed a predominance of single cells with intermixed small, loosely cohesive, three-dimensional cell groups. Cell size was small to intermediate, with round nuclei. There was an overall monomorphic appearance, with minimal nuclear pleomorphism. Chromatin was finely granular and stippled, with multiple, small chromocenters. Cytoplasm in the cell groups had a fibrillary quality and was moderate in amount. Single nuclei were frequently stripped of cytoplasm. Occasional pseudorosettes were noted. Immunocytochemical stains were positive for both neuronspecific enolase and synaptophysin. Ultrastructural examination showed neuritic cell processes with neurosecretory granules and microtubules. Immunoelectron microscopy showed positive labeling of neurosecretory granules by chromogranin A. CONCLUSION: FNA cytomorphology, in combination with ancillary studies, can provide an accurate diagnosis of metastatic ONB.

Cytomorphologic correlates of human papillomavirus infection in the "normal" cervicovaginal smear.

OBJECTIVE: To determine if cytologic abnormalities less striking than those usually considered diagnostic could predict the presence of human papillomavirus (HPV). STUDY DESIGN: Cervical scrapings were obtained from 403 women and examined by conventional Papanicolaou staining and for the presence of low- and high-risk human HPV DNA. The cytologic smears from 63 HPV DNA-positive and 63 matched HPV DNA-negative patients whose smears were initially read as normal or inflammatory were reviewed by a single cytotechnologist and a cytopathologist, who were blind to the HPV result. RESULTS: The cytologic diagnosis was upgraded to atypical squamous cells of undetermined significance (ASCUS) in nine cases and to low grade squamous intraepithelial lesion in one. All 10 upgraded cases were from the HPV DNA-positive group. A review diagnosis of ASCUS was significantly associated with both HPV in general and the presence of high-risk HPV DNA. Partial koilocytosis and multinucleation were associated with the detection of high-risk HPV DNA, while only partial koilocytosis was associated with the presence of low-risk HPV DNA. CONCLUSION: Because infection with high-risk HPV types is associated with cervical neoplasia, partial koilocytosis and multinucleation should be viewed with greater concern and possibly added to the ASCUS definition.

Vimentin-positive spider-shaped Kupffer cells. A new clue to cytologic diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy.

The identification of Kupffer cells highlighted by positive immunostaining for vimentin on direct smears was found to play an important role in the diagnosis of primary and metastatic hepatocellular carcinoma by fine-needle aspiration biopsy. The Kupffer cell, identified by vimentin staining, is spider- or star-shaped with multiple elongated and slender cytoplasmic processes. Direct smears obtained by fine-needle aspiration biopsy from 14 cases of hepatocellular carcinoma and 15 cases of metastatic carcinoma were stained with vimentin. The cytologic diagnoses were verified by histologic and/or clinical follow-up. All 14 cases of hepatocellular carcinoma, including 9 primary and 5 metastatic, contained significant number of vimentin-positive spider cells within tumor clusters. There were at least three spider cells present within each tumor cluster, involving at least 50% of the tumor clusters. The spider cells were not only found in the well-differentiated type but also in the poorly differentiated and pleomorphic large cell types of the hepatocellular carcinoma. However, the tumor cells from 15 metastatic carcinomas contained no or few spider cells in the tumor clusters. The presence of numerous vimentin-positive spider-shaped Kupffer cells within tumor clusters constitutes strong evidence in favor of a diagnosis of hepatocellular carcinoma.

Fine-needle aspiration cytology of islet cell tumors.

Islet cell tumors of the pancreas are neuroendocrine neoplasms whose biologic behavior has been well characterized. Frequently, these tumors produce one or more hormones which may strongly affect the patients' clinical presentation. In this study, we have examined fine-needle aspirates (FNA) from 13 islet cell tumors and have summarized their cytomorphologic appearances. The smears prepared from aspirates of the islet cell tumors displayed loose cellular arrangements and numerous single cells, with most cases demonstrating a predominance of single cells over the loose groups. An important diagnostic feature was the uniform appearance of the neoplastic cells. Nuclei were small to moderate in size, always round to oval in shape, and frequently contained small nucleoli. In 11 cases, the nuclear chromatin pattern was finely granular and evenly-distributed while in two cases the chromatin was coarser. Eccentrically located nuclei were commonly found and binucleated cells were seen in one-half of the aspirates. At least a moderate amount of finely granular cytoplasm was always identifiable. Immunocytochemical stains for neuron-specific enolase were positive in all five of our cases in which staining for this marker was attempted and chromogranin was positive in five of six cases. Generally, our cytomorphologic observations were supported by the findings of other investigators as reported in the cytology literature. The cytomorphologic characteristics of islet cell tumors are distinctive, and appropriate ancillary studies can be used to support the FNA diagnosis of this entity.

Fine needle aspiration cytology of carcinoid tumors.

OBJECTIVE: To define the cytomorphologic features of carcinoid tumor. STUDY DESIGN: The study consisted of 19 carcinoid tumors sampled by fine needle aspiration. These included 6 pulmonary carcinoids. 11 intestinal carcinoids and 2 aspirates from a patient with a mediastinal carcinoid. The cytomorphologic features of carcinoid tumor were documented, and, in selected cases, immunocytochemical findings were noted. Additionally, the cytology literature concerning carcinoid tumor was reviewed and summarized. RESULTS: Morphologically, the carcinoid tumors consisted predominantly of loose groups with a background of single cells. A striking degree of cellular and nuclear monomorphism was seen in all cases. Nuclei were small and round to oval, and all exhibited a characteristic finely granular, evenly distributed chromatin pattern. Cytoplasm was minimal to moderate in amount and finely granular in appearance. Necrosis and prominent nucleoli were not seen. Positive staining was noted in all seven cases in which immunostaining for chromogranin was performed. Neuron-specific enolase was positive in four of five cases. CONCLUSION: The cytomorphologic characteristics of carcinoid tumors are distinctive, and appropriate ancillary studies can assist in confirming the diagnosis.

Fine needle aspiration of medullary carcinoma of the thyroid. Cytomorphology, immunocytochemistry and electron microscopy.

OBJECTIVE: To analyze of medullary carcinoma of the thyroid (MCT) diagnosed by fine needle aspiration (FNA) utilizing cytomorphologic features and ancillary studies. STUDY DESIGN: Nine cases of MCT were collected, and the cytomorphologic findings were reviewed. Additionally, immunocytochemistry, immunoelectron microscopy and ultrastructural examination results were reviewed for selected cases. RESULTS: In five cases, loose groups predominated over single cells, whereas single cells predominated in three cases. One case showed only highly cohesive groups of cells. Most cells were round to oval, and every case had some degree of plasmacytoid morphology. Spindle-shaped cells were predominant in one case and were occasionally noted as a subpopulation in the other cases. Binucleation was noted in seven cases, and scattered, abnormally large nuclei were identified in five cases. The cytoplasm was moderate to abundant and delicate in all cases. Routine immunocytochemical staining for calcitonin and chromogranin was positive in three of four cases, and staining positive for the markers was detected by immunoelectron microscopy in two cases. In four cases, electron microscopy revealed neurosecretory granules. CONCLUSION: The cytomorphologic appearance of medullary thyroid carcinoma is highly distinctive, and the diagnosis can be corroborated by appropriate ancillary studies.

Fine needle aspiration cytology of a male breast carcinoma exhibiting neuroendocrine differentiation. Report of a case with immunohistochemical, flow cytometric and ultrastructural analysis.

We present the cytologic, immunohistochemical, flow cytometric and ultrastructural findings of a case of invasive ductal carcinoma of the breast with features of neuroendocrine differentiation occurring in an 83-year-old male. Fine needle aspiration (FNA) cytology of the patient's tumor demonstrated a markedly cellular specimen to discohesive tumor cells, present primarily singly, with occasional loose groups. The cells were relatively large, with pleomorphic, eccentrically placed, round to oval nuclei. The cytoplasm was abundant and contained prominent red granules (Papanicolaou stain) that were also argyrophilic. Immunohistochemical studies performed on the aspirate and the subsequently excised malignant breast tissue revealed positive staining for neuron-specific enolase, chromogranin A, synaptophysin and gastrin. Also, the majority of the tumor stained positive with antibodies to both estrogen and progesterone hormone receptors. DNA flow cytometry demonstrated an aneuploid stemline population with a DNA index of 1.73 and an S-phase fraction of 4.5%. Electron microscopy was performed on the FNA material, and numerous variable-sized, membrane-bound, dense-core granules diffusely scattered within the cytoplasm of the neoplastic cells were identified. The specific cytologic features of this tumor, along with the immunocytochemical and ultrastructural features, can aid the pathologist in rendering an accurate FNA diagnosis of this specific subtype of breast carcinoma.

Cytologic diagnosis of rhabdomyosarcoma in a patient with germ cell tumor. A case report.

The development of sarcomas in patients with germ cell tumors is rare but has been reported previously. Theories about its pathogenesis include derivation of the tumor cells from pluripotential germ cells and malignant transformation from teratomatous elements. This report describes the occurrence of rhabdomyosarcoma in a patient with a history of mixed germ cell tumor of the testis who developed a malignant pleural effusion. Cytologic evaluation of the fluid revealed single malignant cells with high nuclear/cytoplasmic ratios and prominent nucleoli. While these features initially suggested a diagnosis of metastatic seminoma, careful cytologic and immunohistochemical examination revealed features consistent with metastatic rhabdomyosarcoma. The exfoliative cytologic findings of other germ cell tumors are also discussed.

Endosonography-guided real-time fine-needle aspiration biopsy.

Twenty-six patients were prospectively evaluated with endosonography-guided real-time fine-needle-aspiration biopsy. This cohort comprised 14 patients with a pancreatic mass revealed by CT or a stricture of the main pancreatic duct seen at ERCP, 7 patients with mediastinal lymphadenopathy, 3 patients with extrapancreatic abdominal masses, and 2 patients with subepithelial or infiltrative lesions. Endosonography-guided real-time fine-needle-aspiration biopsy was diagnostic in 18 of 20 patients in whom surgical confirmation was available or in whom malignancy was found and confirmed by clinical follow-up (accuracy of 90%). In the subgroup of patients with pancreatic lesions, 3 had previously undergone nondiagnostic CT-guided fine-needle-aspiration biopsy and 2 did not have evidence of a mass by CT. Real-time fine-needle-aspiration biopsy was diagnostic for malignancy in 4 of these individuals. In the 7 patients with mediastinal lymph nodes, 2 had nondiagnostic transbronchial biopsy and 2 had no evidence of mediastinal lymphadenopathy by CT scan. Endosonography-guided real-time fine-needle-aspiration biopsy diagnosed malignancy in both individuals with nondiagnostic transbronchial studies and was able to identify mediastinal lymphadenopathy in the 2 patients with negative CT scans (malignancy confirmed with real-time fine-needle-aspiration biopsy in 1). Overall, in 9 of 10 lesions in which visualization by CT was not possible (5), CT-guided fine-needle aspiration was unsuccessful (3), or prior nonsurgical biopsy techniques were unsuccessful (2), real-time fine-needle-aspiration biopsy was diagnostic.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholesterol granuloma of the breast: a mimic of carcinoma.

Cholesterol granuloma of the breast is a rare condition that may be related to the common disorder mammary duct ectasia. Its importance is in its tendency to mimic carcinoma clinically and radiologically. The authors report a case in a 65-year-old asymptomatic woman.

Combined endosonography and fine-needle aspiration cytology in the evaluation of gastrointestinal lesions.

Fifty consecutive patients with extrinsic or submucosal masses, gastric ulcers, or surgical anastomoses suspected of malignancy but with previously negative findings on conventional forceps biopsy or brush cytology underwent endoscopic ultrasonography followed by fine-needle aspiration cytology. Diagnostic cytology results were obtained in 37 of 50 (74%) patients. In 11 of the 13 patients with negative fine-needle aspirates, the endosonographic findings supported the final diagnosis as assessed by clinical follow-up or surgical pathology findings. In all patients, endosonography was useful for identifying the extent of the lesion and detailing regional anatomy to permit an assessment of the safest and most appropriate site for needle biopsy. The highest yield was found in evaluating tumors extrinsic to the gastrointestinal tract that were impinging on the lumen (14 of 15 or 93%). In 14 patients who underwent subsequent surgical therapy, the accuracy of fine-needle aspiration cytology was 86% (12 of 14). No complications occurred in any of the patients. EUS combined with fine-needle aspiration cytology appears to be useful in the evaluation of extrinsic or submucosal masses and suspicious appearing ulcerative lesions and surgical anastomoses of the gastrointestinal tract when conventional biopsy and brush cytology techniques have been unsuccessful.

Preoperative staging of non-small cell lung cancer: transesophageal US-guided fine-needle aspiration biopsy of mediastinal lymph nodes.

PURPOSE: To evaluate the usefulness of transesophageal real-time ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) in staging non-small cell lung carcinoma. MATERIALS AND METHODS: Two patients (a 64-year-old man and a 48-year-old woman) with non-small cell lung carcinoma and mediastinal lymphadenopathy detected at computed tomography underwent preoperative evaluation with transesophageal real-time US-guided FNAB. Two aspirates were obtained from each patient. RESULTS: Diagnostic tissue from a contralateral posterior mediastinal lymph node was obtained from the first aspirate in each case. Neither patient experienced a complication as a result of this technique, and both were subsequently referred for palliative therapy in light of these findings. CONCLUSION: Real-time US-guided FNAB is useful in the preoperative staging of disease in selected patients with non-small cell lung cancer.