Laryngeal cytology: A cytological, histological, P16 and human papillomavirus study.

BACKGROUND: Invasive diagnostic methods, such as punch biopsies, have a potential to produce undesirable side effects in the larynx, such as scarring and vocal dysfunction. This study is an attempt to assess the diagnostic potential of cytology to efficiently diagnose premalignant and malignant laryngeal lesions, while sparing patients the risk of complications of punch biopsies. METHODS: Laryngeal smears, using endocervical-type brushes, and punch biopsies were procured from each patient. Smears were prepared and the brush was cut and put in Surepath preservative solution for cytological analysis and human papillomavirus (HPV) DNA testing. A Real-TM Quant kit that detects 14 HPV types was used for genotyping. Immunohistochemical staining for p16 was performed on cytological and histological specimens. RESULTS: Cytological diagnosis was correct in 84.6%, 100% and 100% of cases with a histological diagnosis of squamous cell carcinomas, high-grade squamous intraepithelial lesions and benign lesions, respectively. However, cytological interpretation was correct only in 25% of low-grade squamous intraepithelial lesions. HPV DNA test was positive in only one case, which was a laryngeal polyp. Testing for p16 was negative in all the cytological and histological material. CONCLUSION: Laryngeal cytology is a useful diagnostic tool in establishing the diagnosis of high-grade squamous epithelial cell abnormalities. Recognition of low-grade lesions, however, is challenging. HPV genotyping and p16 staining do not seem to be helpful ancillary techniques in cytological material procured from the larynx.

Perspectives on signet ring stromal cell tumor and related signet ring cell lesions of the gonads.

In this article, we discuss advances in our knowledge of the pathology of signet ring stromal cell tumor and related signet ring cell lesions of the ovary and a single case of signet ring stromal cell tumor of the testis. We divide ovarian signet ring cell lesions into 3 categories that reflect differences in their pathogenesis and histologic appearance. With 1 exception, all authentic cases of signet ring stromal cell tumor have been unilateral. Cases of ovarian signet ring stromal cell tumor from the literature can arise in 2 ways. The majority of cases arise multifocally from fibroma, whereas the remainder likely arise directly from the ovarian stroma. In difficult cases, immunocytochemistry provides improved diagnostic accuracy in distinguishing signet ring stromal cell tumor and its mimics from Krukenberg tumor. The most useful antibodies in this regard are epithelial membrane antigen and vimentin.

Primary retroperitoneal mucinous cystadenoma with a sarcoma-like mural nodule: an immunohistochemical study with histogenetic considerations and literature review.

Primary retroperitoneal mucinous cystadenomas (PRMCs) are extremely rare tumors and their association with sarcoma-like mural nodules (SLMNs) has not been described thoroughly. The aim of this study is to characterize the gross and microscopic features and the immunohistochemical profile of the first case of PRMC with SLMN and to discuss the differential diagnosis of SLMNs. The literature related to primary retroperitoneal mucinous tumors is reviewed in an attempt to clarify the histogenesis of the epithelial and sarcomatoid components of the associated mural nodules. A 34-yr-old woman presented with a 14-cm retroperitoneal cystic lesion with a 6-cm mural nodule. An immunohistochemical study with a panel of 19 antibodies and a histochemical study for mucin stains were performed. The epithelial component of the PRMC showed positive staining for cytokeratin (CK) 7, CK AE1/3, epithelial membrane antigen, carcinoembryonic antigen, and calretinin. The neoplasm was not immunoreactive for CK 20, CK 5/6, and the other antibodies used in this study. In addition, it stained positively for mucin by mucicarmine, periodic acid-Schiff, and Alcian blue. The stromal cells of the cyst showed estrogen receptor positivity. SLMN cells were negative for all CKs and other epithelial markers used in the study, but they showed diffuse positive staining for vimentin and CD68, and positive staining for Ki-67 was demonstrated in 25% of these cells. The immunohistochemical and histochemical profiles of PRMC were similar to those of ovarian mucinous neoplasms and the mesothelium. The formation of SLMNs seems to be related to subepithelial hemorrhage and some reactive epithelial changes near the mural nodules. The specific immunohistochemical and morphologic features of SLMNs are helpful in differentiating them from malignant mural nodules, including true sarcomas, osteoclast-rich undifferentiated carcinomas, and carcinosarcomas. Such a differentiation is critical in view of its significant impact on the management of these neoplasms, particularly in young patients who desire to preserve their fertility.

Primary Synovial Sarcoma of the Thyroid: Challenges in Cytologic Diagnosis and Review of the Literature.

BACKGROUND: Primary synovial sarcoma (SS) of the thyroid (PSST) is extremely rare. Its differential diagnosis from other neoplasms is essential since it has different management protocols and prognosis. CASE: A 26-year-old man with a 4.5-cm solid lobulated mass was seen at an outside hospital. Fine needle aspiration (FNA) was interpreted as a papillary carcinoma, and a total thyroidectomy was performed. The final histologic diagnosis was spindle epithelial tumor with thymus-like differentiation (SETTLE). No metastases were detected at that time, and the patient received radioactive iodine treatment. Two years post-surgery, he was seen at our hospital with a local recurrence, and FNA was considered as consistent with SETTLE. The mass was resected, and a left modified radical neck dissection was performed. The tumor revealed necrosis and a high mitotic index. Following histologic, immunohistochemical, and molecular studies, the tumor was classified as a PSST. The patient received chemotherapy and targeted immunotherapy, but he died 41 months after the initial presentation. CONCLUSION: The main diagnostic pitfall of PSST is SETTLE. The presence of mitotic figures and basal lamina material, negative staining for smooth muscle actin, and positive staining for transducer-like enhancer of split 1 antibody favor SS over SETTLE. SYT gene rearrangement is essential to establish the definitive diagnosis of PSST.

Cytological diagnosis of endocrine tumors of the pancreas by endoscopic ultrasound-guided fine-needle aspiration biopsy.

The aim of this study was to evaluate the efficacy and accuracy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) in the diagnosis of pancreatic endocrine tumors and to analyze their cytomorphology. Between March 1999 and June 2004, a total of 30 patients with a cytological diagnosis of pancreatic endocrine tumors were found. Their records were retrieved and the cytological materials were analyzed. The mean size of the tumors assessed by EUS was 3.0 cm. Immediate preliminary interpretation was rendered after an average of 1.5 passes. Based on the cellular patterns, cases were divided into three categories: loosely cohesive aggregates, discohesive single cells, and cohesive flat sheets. Most tumor cells had abundant cytoplasm and eccentric nuclei. Chromatin was fine or coarse but was evenly distributed in all cases. Nuclear pleomorphism, multinucleation, intranuclear inclusions, mitotic figures, and necrosis were seen. Immunohistochemical (IHC) studies on cell blocks confirmed the diagnosis in all cases. EUS-guided FNA is efficient and accurate in establishing the diagnosis of pancreatic endocrine tumors. The variety of cellular patterns presents several differential diagnostic issues that should be considered to avoid erroneous interpretation.

Thyroid fine-needle aspiration biopsy in children and adolescents: experience with 218 aspirates.

To evaluate the role of fine-needle aspiration (FNA) biopsy of thyroid nodules in pediatric and adolescent patients, the cytology reports of 218 thyroid FNA biopsies performed on children and adolescents ranging from 10 to 21 yr of age were reviewed. The cytology diagnoses were categorized into four groups: unsatisfactory, benign, suspicious, and malignant. One hundred nineteen (54%) of the aspirates were diagnosed as "benign," 20 (9%) were diagnosed as suspicious for malignancy; and 17 (8%) were diagnosed as malignant. Sixty-two (28%) of the aspirates were read as unsatisfactory for interpretation. Sensitivity of thyroid FNA in diagnosing thyroid malignancy relative to final histological diagnoses was 100%, and specificity was 65%. FNA of thyroid nodules in the pediatric and adolescent population is comparably as sensitive and specific as in the adult population. The acceptance of this procedure in the routine evaluation of young patients' thyroid nodules should reduce the number of unnecessary surgeries for benign thyroid disease.

Transitional cell carcinoma of the renal pelvis the diagnostic role of pelvic washings.

One hundred renal pelvic washings were reviewed blindly for 12 cytologic features. Of 52 washings with tissue confirmation, the cytologic diagnosis suggestive of or positive for transitional cell carcinoma (TCC) was made in 36 cases; 11 were negative, and 5 were unsatisfactory. Of 36 positive washings, histology confirmed the TCC diagnosis in 35 but revealed only reactive changes in 1. Of 11 negative washings, 9 were histologically negative for TCC, and 2 were positive for high-grade TCC. Among 48 washings without tissue confirmation, 33 were negative for TCC or showed reactive changes, 12 were negative for high-grade dysplasia or malignancy, but low-grade TCC could not be ruled out, 1 was suggestive of malignancy, and 2 were unsatisfactory. Clinical follow-up revealed no TCC. Predictive cytologic features of high-grade TCC were high nuclear/cytoplasmic ratio, isolated cells, anisonucleosis, nuclear hyperchromasia, and coarse chromatin; for low-grade they were presence of more than 5 papillary groups, cellular overlapping, anisonucleosis, and hyperchromasia. The sensitivity and specificity for the cytologic diagnosis were 89% and 97% for high-grade TCC and 100% and 78% for low-grade TCC, respectively. Renal pelvic washings can be used to accurately diagnose TCC of the renal pelvis. The positive predictive value for high-grade TCC is 93%, but for low-grade tumors it is 43%.

Large B-cell lymphomas: fine-needle aspiration plays an important role in initial diagnosis of cases which are falsely negative by flow cytometry.

Large B-cell lymphomas (LBCLs) have significant false-negative results when immunophenotyped by flow cytometry (FC). To clarify the role fine-needle aspiration (FNA) in reducing this false-negative rate, 28 cases ultimately diagnosed as LBCL that had FNA as part of the workup and a negative FC were identified. We examined their clinical and cytologic features, in comparison with cases of LBCL with FNAs that were positive by FC. In 24/28 FC-negative cases (86%) a cytologic diagnosis of suspicious or positive for malignancy was rendered. We conclude that cytologic analysis is more sensitive than FC in the diagnosis of malignancy in FNA of LBCL, particularly in aspirates with low cellularity and/or low viability. Examination of cytospin preparations of the actual material analyzed by FC may provide an indication that an FC result is falsely negative. It is important to recognize the potential of false-negativity by FC of LBCLs when interpreting FNAs with features suggesting lymphoma.

Glandular lesions of the cervix on thin-layer Pap tests. Validity of cytologic criteria used in identifying significant lesions.

OBJECTIVE: To determine the cytologic features that are most helpful in characterizing significant glandular lesions of the cervix observed on the ThinPrep (TP) Pap test (Cytyc Corp., Boxborough, Massachusetts, U.S.A.) and to compare these features with those published for conventional smears. STUDY DESIGN: Thirty-nine TP preparations with cytologic evidence of glandular lesions of the cervix and histologic and/or clinical correlation were studied. These lesions included (1) 11 cases of benign/reactive conditions; (2) 10 cases of adenocarcinoma in situ (AIS), of which 1 had both AIS and carcinoma in situ; (3) 1 case of invasive adenocarcinoma; (4) 15 cases of squamous intraepithelial lesions and squamous cell carcinoma, including 4 with glandular involvement, and (5) 2 cases of adenosquamous cell carcinoma. These cases were reviewed by the first author without knowledge of the histologic diagnosis. Twenty-five previously published cytologic criteria were used to evaluate glandular cells on TP slides. Statistical analysis was performed using Fisher's exact test to determine the significance of the features studied. RESULTS: All glandular lesions had cytologic features on TP similar to those previously described on conventional smears. However, TP slides demonstrated enhanced nuclear features but less-preserved architectural patterns. Reactive lesions showed minimal overlapping without hyperchromasia or mitotic figures and with normal nuclear/cytoplasmic ratios. AIS and invasive adenocarcinoma cases had similar features. Increased cellularity and overcrowding were prominent, whereas feathering, rosettes and cell strips were present but subtle. CONCLUSION: Glandular lesions of the cervix on TP slides shared many of the characteristic features reported for conventional smears. However, nuclear details were more pronounced in TP slides, while architectural patterns, although present, were relatively subtle.

Signet ring stromal cell tumor revisited and related signet ring cell lesions of the ovary.

In this article, we revisit the first reported case of ovarian signet ring stromal cell tumor (SRSCT) using modern immunohistochemical techniques and compare it to a case of signet ring cell transformation of lutein cells in an ovarian stromal tumor having components of luteinized thecoma and sclerosing stromal tumor. We introduce a new classification of signet ring stromal cell lesions of the ovary that serves as a framework to distinguish pathogenetically distinct ovarian stromal lesions that may be confused with cases of true SRSCT. The SRSCT in our first case most likely arose directly from the ovarian stroma without an identifiable precursor neoplasm. In our second case, the association of the signet ring cells with lutein cells and the positive staining of the signet ring cells for inhibin and steroidogenic factor 1 confirm that in some instances signet ring cells are derived from lutein cells.

Reduced annexin II protein expression in high-grade prostatic intraepithelial neoplasia and prostate cancer.

CONTEXT: Annexin II is a calcium-dependent phospholipid-binding protein that plays a role in many cellular functions, including apoptosis, signal transduction, and cellular motility. The protein is strongly expressed in normal prostatic epithelial glands, but its expression in benign prostatic lesions has not been reported. Although commonly underexpressed in prostate cancer, the association of reduced expression with pathologic grade and stage is unknown. OBJECTIVE: To compare annexin II expression in benign prostatic lesions with expression in high-grade prostatic intraepithelial neoplasia and prostate cancer, as well as to correlate expression levels with pathologic grade and stage. DESIGN: A semi-quantitative assessment of annexin II expression was performed in radical prostatectomy specimens from 74 patients and prostate needle core biopsy specimens from 13 patients. Foci with normal prostatic glands, atrophic glands, basal cell hyperplasia, high-grade prostatic intraepithelial neoplasia, and prostatic adenocarcinoma were evaluated. RESULTS: Annexin II expression was present in more than 50% of glands in most (>85%) samples of benign prostatic epithelium, atrophic glands, and basal cell hyperplasia. In high-grade prostatic intraepithelial neoplasia, annexin II staining was markedly reduced in epithelial cells but not in basal cells. Annexin II was absent or focally present in moderately differentiated adenocarcinoma but was retained in poorly differentiated adenocarcinomas. CONCLUSIONS: Reduced annexin II expression may be a useful diagnostic biomarker to help identify small foci of moderately differentiated adenocarcinoma on needle core biopsy specimens since it is consistently expressed in benign prostatic glands. Re-expression of annexin II in poorly differentiated adenocarcinoma may provide prognostic information.

Intraoperative consultation in gynecologic pathology.

CONTEXT: Gynecologic specimens are commonly submitted for intraoperative consultation, primarily to confirm the presence and histologic type of malignancy, as well as to determine the adequacy of resection by examining the surgical margins. OBJECTIVE: To review and discuss the application, indications, contraindications, and limitations of intraoperative consultation regarding gynecologic specimens, as well as the causes of false-positive or false-negative frozen section results. DATA SOURCES: Review of the pertinent literature and the authors' expertise and experience. CONCLUSIONS: In most instances, intraoperative consultation regarding gynecologic specimens accurately determines the type of malignancy, the status of the resection margins or the lymph nodes, and the extent and depth of involvement by a tumor. Although the pathologist and the surgeon must be aware of the limitations, the use of intraoperative consultation represents a highly sensitive and specific technique that can play a critical role in the management of gynecologic disease.

The utility of p16INK4a and Ki-67 staining on cell blocks prepared from residual thin-layer cervicovaginal material.

BACKGROUND: Cell blocks can be prepared from residual thin-layer cervicovaginal (ThinPrep) material and can be used in immunohistochemical staining assays for p16INK4a and Ki-67, which are surrogate markers related to human papillomavirus infection and cell proliferation, respectively. The objectives of the current study were 1) to investigate the feasibility and the role of cell block preparations in identifying significant neoplastic and preneoplastic lesions of the uterine cervix and 2) to assess the feasibility of using p16INK4a and Ki-67 immunohistochemical staining patterns on cell blocks to identify significant preneoplastic cervical lesions. METHODS: Cervicovaginal cytology specimens from 85 patients were analyzed. Cytologic diagnoses based on ThinPrep Papanicolaou test results were as follows: squamous cell carcinoma was diagnosed in 3 specimens, high-grade squamous intraepithelial lesions (HSIL) were diagnosed in 27 specimens, low-grade squamous intraepithelial lesions (LSIL) were diagnosed in 20 specimens, and atypical squamous cells of uncertain significance (ASCUS) were diagnosed in 11 specimens. Diagnoses of negativity for intraepithelial lesions or malignancy (NILM) were made in 24 specimens. Cell block sections were stained with hematoxylin and eosin and were immunostained with antibodies against p16INK4a protein and Ki-67 antigen. RESULTS: The cytomorphologic diagnoses made using cell block preparations were as follows: SCC in 2 specimens, HSIL in 20 specimens, LSIL in 30 specimens, NILM in 32 specimens, and no diagnosis in 1 specimen. In 62 cases (73%), the diagnoses made using cell block preparations were in agreement with the ThinPrep diagnoses. Immunostaining of cell blocks for p16INK4a and Ki-67 exhibited a statistically significant association (P < 0.05) with the presence of significant lesions on either cell block or ThinPrep analysis. CONCLUSIONS: To the authors' knowledge, p16INK4a has not been analyzed previously in ThinPrep cell blocks, and the correlation between Ki-67 expression and cell block diagnoses also has not been reported previously. The current results indicate that cell blocks prepared from residual ThinPrep material represent an additional reliable diagnostic tool in the evaluation of cervical samples. Furthermore, immunohistochemical studies may be helpful in differentiating significant preneoplastic changes from other cervical lesions, such as atrophy.

Parathyroid cytology: avoiding diagnostic pitfalls.

BACKGROUND: Interpretation of parathyroid fine-needle aspirates (FNA) remains problematic not only because this type of specimen is rare but also because the pertinent literature is very limited. We systematically reviewed parathyroid FNAs in our files and sought to delineate additional diagnostic criteria. DESIGN: Review of all thyroid and parathyroid aspirates from January 1990 to June 1998 disclosed 12 parathyroid lesions. The final diagnoses included four parathyroid adenomas, one intrathyroidal hyperplastic parathyroid, one intrathyroidal parathyroid adenoma, one atypical parathyroid adenoma (all confirmed by histologic screening or immunocytochemistry), and five parathyroid cysts (all confirmed by immunoassay). Papanicolaou and Diff Quik-stained smears of the parathyroid FNAs were reviewed. The cytologic features were compared and contrasted with those of thyroid FNAs to establish criteria for differential diagnoses. RESULTS: The FNAs of the five parathyroid cysts yielded virtually acellular fluid with a characteristic water-clear appearance and markedly elevated levels of parathyroid hormone. The remaining seven aspirates consisted of moderately cellular smears that showed an admixture of architectural features. Common patterns included cohesive three-dimensional groups, disorganized sheets, papillary fragments, microfollicles, and a single case showing lymphoidlike smears. Although the cells were generally small and round to oval, all cases demonstrated mild to moderate anisokaryosis. The nuclei were hyperchromatic E with coarsely granular chromatin reminiscent of that of small lymphocytes. Occasional nucleoli were noted. Although the cytoplasm was usually pale blue and finely granular with ill-defined borders, two cases showed well-delineated cytoplasmic membranes. Less common findings included cytoplasmic granulation, vacuolization, and rare oxyphilic cells. Naked nuclei were noted in the background of all of the aspirates to varying degrees. Other background findings included the presence of colloidlike material, macrophages, and lymphocytes. One interesting finding that to date has not been reported is the presence of nuclear overlapping (100%) and nuclear molding (71%), which is an uncommon finding in thyroid aspirates. CONCLUSIONS: FNAs of the parathyroid can be easily confused with that of the thyroid, not only because of the clinical similarity between these two types of lesions but also because of the overlap in cytomorphologic features of the aspirated cells. Although no one single cytomorphologic feature is diagnostic, a combination of cytologic parameters noted earlier should raise the possibility of a parathyroid lesion. Aspirates of parathyroid cysts show acellular water-clear fluid with elevated parathyroid hormone measurements.