Argyrophilic nucleolar organiser regions (AgNORs) in breast lesions

Nucleolar organiser regions (NORs) demonstrated by argyrophilia of NOR-proteins are indicator of cellular proliferative activity. The NORs can be identified in the nuclei as brown or black dots with silver colloidal staining technique in formalin fixed paraffin sections and in cytology smears. Seventy-five cases including 45 tissue sections and 30 fine needle aspiration cytology (FNAC) smears of benign and malignant lesions of breast have been studied to evaluate the significance and practical application of AgNOR count per nucleus. Out of 45 tissue sections 15 belonged to fibrocystic disease, 10 fibro-adenomas and 20 carcinomas and of the 30 FNAC smears, 10 were fibrocystic disease, 8 fibro-adenomas and 12 carcinomas. In fibrocystic disease the mean AgNOR count was 1.60 (FNAC group-0.75, tissue section-1.61). In fibro-adenomas it was 1.61 (FNAC-1.63, tissue section-1.59). The mean count in carcinoma was 12.10 (FNAC-12.08, tissue section-12.10). The difference in AgNOR count in fibrocystic disease and fibro-adenoma was not significant, but that between benign breast lesion and carcinoma was significant. No difference was observed between FNAC and tissue section groups in benign or malignant lesions. The simple staining technique can be used as an additional criterion to differentiate the benign and malignant lesions of breast.     

Diagnostic pitfalls of fine needle aspiration cytology for breast disease

We analysed 1500 consecutive fine needle aspiration cytology (FNAC) specimens to ascertain the reasons for diagnostic failure. Of 221 tumours proven malignant following open biopsy, 184 (83%) were correctly diagnosed on FNAC. Of 1082 aspirates classified 'benign', 787 (73%) underwent open biopsy and of these 33 (4%) were diagnosed malignant. All three cases of ductal carcinoma in-situ (DCIS) and eight of 16 lobular carcinomas in this study were missed using FNAC alone. Twelve of the 22 patients with invasive carcinoma not diagnosed on cytology had tumours measuring less than 1 cm diameter. Six of 1500 FNAC reports (0.4%) gave false positive diagnoses, five were classified as 'suspicious of malignancy; and one as 'frankly malignant'. The overall sensitivity was 84%, specificity 99% and positive predictive value 97%. Though these results confirm the value of FNAC as a rapid means of diagnosing most breast cancers, it it unreliable in patients with invasive carcinomas less than 1 cm in diameter and for the detection of lobular and in-situ carcinoma.     

Aberrant tau phosphorylation and neurite retraction during NGF deprivation in PC12 cells

OBJECTIVE: To investigate the final results of cases with preoperative diagnoses of thyroid follicular neoplasms by fine needle aspiration cytology (FNAC). STUDY DESIGN: A retrospective review of 6,499 patients who received thyroid ultrasonography with FNAC at Chang Gung Memorial Hospital. Among 6,499 patients, 209 (3.2%) were diagnosed by FNAC as having follicular neoplasms, of which 84 received surgical treatment. Eighty-two of the 84 cases had a frozen section prepared during the operation. RESULTS: Thyroid malignancy was confirmed histopathologically in 164 cases. Among 84 thyroid follicular neoplasm patients, 21 cases were diagnosed as malignant tumors, including papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma and Hürthle's cell carcinoma. Ultrasonography on these 21 patients revealed that 16 cases (76.2%) had low echo density in the thyroid nodule. The percentage was statistically significantly different from that in benign cases, 23.8% (P < .05). A higher incidence of malignancy was found in males, but the data did not reach statistical significance (P = .0586). CONCLUSION: Most of the follicular neoplasms revealed by FNAC were benign lesions. Low echo density on ultrasonography and male sex carried a higher risk of malignancy.     

Diagnosis of occult thyroid carcinoma by thyroid ultrasonography with fine needle aspiration cytology

OBJECTIVE: To assess the role of ultrasonography and fine needle aspiration cytology (FNAC) in preoperative diagnosis of patients with occult thyroid carcinoma (OTC). STUDY DESIGN: Data on 768 thyroid carcinoma patients receiving primary treatment at Chang Gung Medical Center were retrospectively reviewed. Of these patients, 97 had OTC. To detect small thyroid nodules early and define the characteristics of clinically palpable nodules, thyroid ultrasonography with FNAC were performed on 67 histopathologically proven OTC patients. Analysis for diagnostic value was done for ultrasonography and FNAC. RESULTS: In the 67 patients receiving ultrasonography with FNAC, 23 were preoperatively diagnosed as having papillary thyroid carcinoma and 1 as having follicular carcinoma. The tumor size of these 24 preoperative FNAC-proven OTC was 0.81 +/- 0.23 cm (mean +/- SD). In the remaining patients, 10 presented pictures suspicious for malignancy, with a mean tumor size 0.63 +/- 0.24 cm, and 33 (49.3%) were diagnosed as having benign thyroid lesions in preoperative FNAC. The tumor size in these 33 lesions was 0.58 +/- 0.24 cm. Fifty-seven of the 67 OTC patients received frozen sections. Thirty-eight papillary thyroid carcinomas and four follicular carcinomas were correctly diagnosed on frozen sections. CONCLUSION: Although the rate is not high, high-resolution ultrasonography and FNAC is the best approach to preoperative diagnosis for OTC patients today.     

Electron microscopic immunolocalization of caltrin proteins in guinea pig seminal vesicles

We report here on five new cases of solid and cystic papillary neoplasm (SCPN) of the pancreas diagnosed by fine-needle aspiration cytology (FNAC). All cytologic samples were obtained by ultrasonography, and the smears were conventionally fixed and stained. Special histochemical and immunocytochemical stains were also performed in some samples. Cytology revealed in all but one case numerous pseudopapillary structures composed of fibrovascular stalks lined with one or more layers of bland-appearing, uniform tumor cells. The tumor cells had round-to-oval euchromatic nuclei with frequently folded smooth contours and one or two small nucleoli. Their cytoplasm often contained eosinophilic, PAS-positive, and diastase-resistant inclusions. Foamy cells, psammoma bodies, blood, and cellular debris were found in the background. The criteria for the differential diagnosis versus other pancreatic lesions are discussed in some detail, as is the role of immunocytochemistry (ICC). In the literature, only 28 cases of cytologically investigated SCPN have been reported to the best of our knowledge. The most helpful criteria for the conclusive identification of SCPN by FNAC include the pseudopapillary arrangement with bland-appearing tumor cells, and, especially, the finding of acidophilic, PAS-positive, and diastase-resistant cytoplasmic granules.     

Ultrasonographically-guided fine-needle aspiration cytology in the diagnosis of colonic lesions

BACKGROUND: The use of fine-needle aspiration cytology (FNAC) in the diagnosis of colonic lesions was investigated. METHODS: Some 22 patients (median age 71 years) with a colonic lesion identified on abdominal ultrasonography underwent ultrasonographically-guided FNAC using a 21-G needle. The sample was checked immediately by a cytopathologist for adequacy. RESULTS: Eighteen patients had colonic carcinoma; aspiration cytology detected malignant epithelial cells consistent with colonic carcinoma in 17 patients and severely dysplastic cells in one patient. The sensitivity and specificity of ultrasonographically-guided FNAC in the diagnosis of colonic carcinoma was 94 and 100 per cent respectively. The remaining four patients had a diagnosis of ileocaecal tuberculosis, ileocaecal Crohn's disease, and metastatic adenocarcinoma in the liver with no identifiable primary (two patients). One demonstrated granulomata, grew acid-fast bacilli and the patient was treated for tuberculosis. One had inflammatory cells and the patient was found to have Crohn's disease on histology. The remaining two patients had confirmed metastatic adenocarcinoma in the liver on aspiration cytology but suspected colonic lesions were found to be benign on cytological examination and no primary lesion was subsequently demonstrated. There were no complications of FNAC and patients complained of minimal discomfort. There has been no evidence of tumour recurrence with a median follow-up of 12 (range 1-25) months. CONCLUSION: Ultrasonographically-guided FNAC is a valid method for the diagnosis of colonic tumours.     

Ultrasound guided percutaneous fine needle aspiration cytology of pancreas: a review of 61 cases

The study includes 61 cases which were subjected to ultrasound (US) guided fine needle aspiration cytology (FNAC) to find out the utility of this technique in the diagnosis of pancreatic lesions. Age of the patients ranged from 23 to 85 years with a median of 50 years. Male to female ratio was 36:25. One or more clinical diagnoses were offered in 16 and in 9 of these, the disease was related to pancreas. Subsequent to US, the lesions were localized to pancreas in 57 and the nature of pathology in the pancreatic lesion could be diagnosed in 31. By FNAC, 31 cases (50.8%) were diagnosed to have pancreatic malignancy which included adenocarcinoma (23 cases), papillary cystic tumour (1), muco-epidermoid carcinoma (1), acinic cell carcinoma (1), islet cell tumor (1), and non Hodgkin lymphoma (4). FNAC of liver in 2 cases and retroperitoneal lymph node in a case of pancreatic adenocarcinoma revealed metastasis. During follow up, 1 case of non Hodgkin's lymphoma showed CSF involvement. Three cases (4.9%) were suspected to have epithelial malignancy of which one was confirmed as an adenocarcinoma following surgery and histology. Four (6.6%) were benign lesions which included nonspecific inflammation (2 cases), tuberculous pancreatitis (1) and pseudopancreatic cyst (1). The remaining 23 cases (37.7%) had normal or inadequate cytology. Of these, FNAC of liver showed metastasis in 2 cases and one case each were diagnosed as adenocarcinoma and pseudopancreatic cyst respectively following surgery. None of the patients had any complication following FNAC. We recommend US guided FNAC to be routinely used for diagnosis of pancreatic lesion.     

FNAC guided by computed tomography in the diagnosis of primary pancreatic adenosquamous carcinoma. A report of three cases

BACKGROUND: Pancreatic adenosquamous carcinoma (ASqC) is an unusual histologic subtype of nonendocrine neoplasia of the pancreas. Although fine needle aspiration cytology (FNAC) is now accepted as a reliable procedure for the diagnosis of pancreatic malignancies, many of these unusual tumors are still diagnosed after surgery or at necropsy. CASES: Between January 1995 and July 1996, 3 of 35 primary pancreatic malignant tumors were diagnosed as ASqC based on computed tomography-guided FNAC. After cytologic diagnosis, all three patients were treated with neoadjuvant chemotherapy and radiotherapy. Two patients completed the treatment and underwent a surgical pancreatic-duodenectomy with antrectomy. The remaining patient is currently under treatment. That patient had a highly infiltrative pancreatic mass that affected the muscular small bowel wall. An endoscopic biopsy was performed. The cytologic diagnosis was confirmed by histology in all cases. Immunohistochemically both components, squamous and glandular, showed reactivity for several keratins, while only the glandular pattern was reactive with carcinoembryonic antigen (CEA). CONCLUSION: FNAC is an accurate, rapid and sensitive tool in the diagnosis of ASqC of the pancreas. We recommend a careful search for both malignant components. Immunoreactivity for CEA can be of help in the detection of the glandular component of this tumor.     

Fine needle aspiration cytology of tubular carcinoma of the breast

OBJECTIVE: To analyze six cases of tubular carcinoma involving the breast in which the diagnosis was made by fine needle aspiration cytology (FNAC). STUDY DESIGN: All patients were females between the ages of 28 and 67 years. The aspiration findings were confirmed by subsequent cell blocks of the aspirates and tissue examination of the breast mass. The aspirate was obtained using multiple passes in the breast masses while maintaining negative pressure. RESULTS: The cytohistologic features in all cases were characterized by a bland and orderly appearance of cells, few cell atypias, variable numbers of myoepithelial cells, tubular structures and somewhat angular epithelial clusters. The value of immunocytochemical study in the diagnosis was uncertain. CONCLUSION: The uncommon occurrence of tubular carcinoma of the breast, the bland and orderly appearances of cells in FNAC samples (as in tissue) and the difficulties in the cytodiagnosis can be found in other breast conditions. A cautious attitude toward the diagnosis of tubular carcinoma from FNAC samples is necessary, and cell atypias, when seen, should be reported with a recommendation for removal of the breast lump for detailed tissue examination.     

Detection of heterozygosity loss in microdissected fine needle aspiration specimens of breast carcinoma

OBJECTIVE: To use the polymerase chain reaction (PCR) to detect loss of heterozygosity (LOH) in microdissected cells form cytologic smears obtained by fine needle aspiration (FNA) from 20 cases of invasive breast carcinoma. STUDY DESIGN: In each case, histologic sections of the primary tumor were also available. Tumor and nontumor cells were dissected from both the cytologic smear and tissue section in all cases except in three smears that showed only tumor cells. RESULTS: LOH was identified in 10 of 19 informative cases using two polymorphic DNA markers at chromosome 11q13 (INT-2, PYGM). The same results were obtained in both the cytologic and histologic specimens, including three cases that had hypocellular cytologic smears. CONCLUSION: FNA of breast lesions provides adequate samples for direct microdissection of the cytologic smear to detect LOH using PCR amplification.     

Fine needle aspiration cytology of oral and pharyngeal lesions. A study of 45 cases

Forty-five patients with oral or pharyngeal swellings were subjected to fine needle aspiration cytology (FNAC) of the mucosal surface over eight years. The age of the patients ranged from 2 to 85 years. The male:female ratio was 25:20. The common sites of involvement were palate (16 cases), cheek (9), pharynx (7) and tonsillar/peritonsillar area (6). Tongue, maxilla, alveolus and lips were less frequently involved. FNAC played an important role in differentiating inflammatory from neoplastic lesions and also benign from malignant neoplasms. Fifteen cases were cytologically diagnosed as benign neoplasms and included pleomorphic adenoma (11 cases), schwannoma (2), odontogenic tumor (1) and benign neoplasm not otherwise specified (1). Sixteen cases were diagnosed as malignancies. There were seven cases of malignant salivary gland tumors and 6 of squamous cell carcinoma. Two cases were high grade non-Hodgkin's lymphomas, and one was malignant odontogenic tumor. Of the 11 inflammatory or reactive lesions, 4 were found to be harboring Actinomyces. The rate of inadequate sampling was 6.7%. Histopathology reports on excised tissue were available for 10 cases only. Seven of nine cases with adequate cytology (77.88%) showed complete agreement with histology.     

Career by choice, not by chance

OBJECTIVE: To analyze the effects of a prospective peer review program on diagnostic accuracy in a routine cytopathology laboratory. STUDY DESIGN: For the study, 4,836 consecutive cases subjected to fine needle aspiration cytology (FNAC) over a one-year period were used. Nine pathologists performed both reporting and peer review functions. Disagreements were classified into "diagnostic errors" and "diagnostic discrepancies," depending on their impact on patient care. The effect of this review on turnaround time was statistically analyzed. A retrospective review of 4,025 cases from the preceding year was performed for comparison. RESULTS: Sixty-six cases with diagnostic disagreements were detected by prospective review. There were 28 diagnostic errors and 38 diagnostic discrepancies. The initial turnaround time for diagnostic FNAC in 90% of total cases was < 24 hours; mean delay for the remainder was 3.3 days. Prospective peer review added a further delay of 1 and 1.5 days, respectively. The number of diagnostic disagreements was significantly higher in the retrospective review (P < .01). CONCLUSION: Prospective peer review of diagnostic FNAC resulted in improved accuracy of diagnosis and reduced potential for inappropriate therapy; however, turnaround time was significantly increased.     

Breast metastasis of cervical carcinoma diagnosed by fine needle aspiration cytology. A case report

BACKGROUND: Metastatic disease of the breast is often an unexpected diagnosis in a female presenting with a breast mass. The most common metastatic cancer to involve the breast is melanoma. Among gynecologic tumors, the most common primary is ovarian carcinoma. Carcinoma of the cervix metastasizing to the breast is extremely rare. CASE: A 45-year-old female developed multiple bilateral breast masses during a course of radiotherapy for carcinoma of the cervix. Cytologic smears of the breast masses revealed adenocarcinomatous cells as well as keratinizing and nonkeratinizing malignant squamous cells, consistent with a histopathologic diagnosis of metastasizing adenosquamous carcinoma of the breast from primary cervical cancer. CONCLUSION: Fine needle aspiration cytology diagnosis of malignancy metastatic to the breast is important to differentiate it from a second primary tumor and avoid an unnecessary mastectomy.     

Establishment of transgenic mice carrying human fetus-specific CYP3A7

OBJECTIVE: To determine the value of cytology in the follow-up of cervical cancer. STUDY DESIGN: The study group consisted of 230 patients with invasive cervical carcinoma who were followed for one to seven years. Forty-four patients developed recurrences or metastases. During this period, cytologic investigations involved 795 exfoliative smears from the cervix or vaginal vault, 10 fine needle aspirates and 5 fluids. RESULTS: Thirty-three patients had positive or inconclusive cervical or vault smears that were histologically proven to be recurrences, and the other 11 patients had clinically obvious recurrences that were not smeared. Cytology first alerted the clinicians to recurrence in eight patients. Of 25 cervical or vault smears reported as malignant, 24 (96%) were histologically confirmed, and 1 showed radiation change on biopsy. In all 22 cases of smears reported as inconclusive, a biopsy followed, and in 9 (41%) of these, recurrence was demonstrated histologically. Inability to distinguish radiation change from recurrent malignancy was the chief cause of inconclusive smears. Five fluids and seven fine needle aspirates were diagnosed as malignant, saving patients an invasive diagnostic procedure. CONCLUSION: Cytology is a useful, cost-effective, noninvasive and accurate investigation in the follow-up of cervical cancer.     

Two-dimensional electrophoretic analysis of membranous protein from human thyroid tissues and cancer cell lines

Thyroid neoplasm is the most commonly encountered neoplastic disorder in endocrine clinics. Thyroid scan, ultrasonography, and fine needle aspiration cytology (FNAC) are used as diagnostic tools to differentiate a malignant nodule from a benign lesion. There are certain limitations and pitfalls in FNAC, especially in the diagnosing of follicular tumors. The lack of characteristic findings or a specific tumor marker are the most common problems in the preoperative diagnosis of thyroid follicular carcinoma. Although serum thyroglobulin level has been used as a tumor marker for post-operative, well-differentiated thyroid cancer, the assay cannot be used for preoperative diagnosis of thyroid carcinoma. In this study, various thyroid tissues and cancer cell lines including CGTH W-1, CGTH W-3, RO 82 W-1, SW 579 cell lines were used for the investigation of tumor markers. Specific spots were identified in the area near the 60 kDa molecular mass protein and isoelectric point (pI) 5.9 of the CGTH W-1 cell line. These spots could not be found in the papillary or anaplastic thyroid cancer cell lines. Another spot with a molecular weight of about 9.8 kDa with a low pI of 4.8 was present in the CGTH W-1 and RO 82 W-1 cell lines. This spot appeared to be a tumor marker of follicular cancer cells. This spot could not be found in the papillary and anaplastic cancer cell lines and other benign thyroid tissues. Specific proteins that were identified in this study may be useful as tumor markers for follicular thyroid carcinoma.     

Coiled-coil domains in proteins secreted by type III secretion systems

STUDY OBJECTIVE: To evaluate the immediate cytologic assessment during CT-guided fine-needle aspiration cytology (FNAC) in the diagnosis of operable indeterminate solitary pulmonary nodules (SPNs). DESIGN: Prospective randomized study. PATIENTS AND METHODS: Two hundred twenty patients with SPN undergoing CT-guided FNAC were divided into two groups. In the first one (group A, 110 patients), a cytologist assessed the adequacy of the sample obtained immediately, and when the sample was considered inadequate, fine-needle aspiration (FNA) was repeated. In the second group (B, 110 patients), an immediate cytologic examination was not performed, but only a gross assessment by the surgeon. Histologic study of the SPN was possible in 217 cases, whereas three patients were followed up radiologically. RESULTS: Adequate samples were obtained in 100% of group A and 88% of group B (p<0.001). The diagnostic accuracy was 99% in group A and 81% in group B (p<0.001). Group A required a mean of 1.22 FNAs compared with 1.10 in group B (p=0.015). The rate of pneumothorax in the whole series was 24%, and statistically significant differences between the two groups were not detected. CONCLUSIONS: Immediate cytologic study significantly increased the adequacy and diagnostic accuracy of CT-guided FNAC of indeterminate SPNs without causing a significant increase of complications.     

Fine needle aspiration cytologic findings in malignant small cell tumor of the thoracopulmonary region (Askin tumor)

From 1980 to 1992, five cases of Askin tumor were diagnosed by fine needle aspiration cytology at the Shiraz University Hospitals, Namazi, Faghihi and Beheshti, Iran. All patients were female, their ages ranging between 15 and 22 years. Three of them had a mass on the right side and two on the left side of the chest. Chest roentgenography revealed no bone involvement. Two tumors involved the lungs and pleura. Urinary catecholamine levels were within normal limits. The fine needle aspiration smears revealed many small, round malignant cells with indistinct cytoplasm, a high nuclear/cytoplasmic ratio and prominent, multiple nucleoli. Homer-Wright rosettes were seen frequently. The cells were often arranged in rows simulating rouleaux formation. They were positively stained by periodic acid-Schiff stain. The histologic sections confirmed the cytologic diagnosis of Askin tumor. Four of the patients died within 7-11 months after treatment began.     

Delayed lumbar epidural hematoma. Discussion of the risk factors: hypertension, anticoagulation and spinal anesthesia]

We report a case of intracystic papillary carcinoma of the breast in a 62-year-old Japanese man, who came to our hospital complaining of a right subareolar mass. Imaging diagnosis was a cyst with an intracystic component. Since repeated aspiration biopsy cytology was interpreted as a borderline lesion, no additional treatment had been given. Because he wanted the removal of the mass 14 months after his first visit, an excisional biopsy was performed under local anesthesia. Pathological examination revealed the intracystic component to be non-invasive papillary carcinoma. Although the incidence of male breast cancer is approximately 1% of all breast cancer, intracystic papillary carcinoma in the male is very rare. From a review of the literature on this disease in Japanese men, an intracystic component can often be demonstrated by ultrasound. However, it is difficult to confirm malignant cells by aspiration biopsy cytology of cyst fluid. Since some cases have a local relapse, excisional biopsy and long-term follow-up are indicated.     

Possible relation of osteopontin to development of psammoma bodies in human papillary thyroid cancer

Fine-needle aspiration cytology (FNAC) is the most useful procedure for the evaluation of thyroid nodules. The requirement for repeated aspirations in the follow-up of benign nodular thyroid disease, however, is controversial. To determine the value of re-aspirations in benign nodular thyroid disease, we studied 457 fine-needle reaspirations performed on 216 patients (197 female, 19 male) aged 42.9+/-12 years with uninodular (n = 65) and multinodular (n = 151) thyroid disease. Two hundred fifty-seven of these were second, 137 were third, 46 were fourth, and 17 were fifth re-aspirations of the same nodule, performed in a mean follow-up time of 43.9+/-31 (3-156) months. FNAC results were benign in 407 (89%), insufficient for diagnosis in 31 (6.8%), suspicious in 16 (3.5%), and papillary carcinoma (PC) in 3 (0.7%). An initial benign diagnosis did not change after multiple aspirations in 213 (98.61%) of the cases. Three patients with initial aspirations read as benign had a diagnosis of PC from their second biopsies, (diagnosis confirmed at surgery). Re-examination of the initial FNAC revealed atypical features in 1 of the 3 patients. These 3 patients likely represent a false-negative result of the initial FNAC rather than benign nodular disease transformed to a malignant one during the follow-up period. In conclusion, a second aspiration of clinically suspicious nodules may correct a few initial false-negative results, but routine additional re-aspirations are not useful for clinically stable disease.