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Biomedical subjects

Ritu Nayar

Publications and source records attributed to Ritu Nayar.

At least 19 recordsLinked to original sources
PubMed2007

The Bethesda Interobserver Reproducibility Study (BIRST): a web-based assessment of the Bethesda 2001 System for classifying cervical cytology.

BACKGROUND: The Bethesda System (TBS) along with its companion atlas was updated in 2001 to improve standardization, clarity, and reproducibility of cervical cytology reporting. METHODS: The authors used a novel web-based format to compare assessments of 77 images demonstrating a range of classical and borderline cytologic changes by a self-selected group of United States cytotechnologists (n = 216) and pathologists (n = 185). RESULTS: Participants were highly experienced, with 71.2% of cytotechnologists and 53.0% of pathologists reporting >10 years of practice. The mean percentage of exact agreement with the panel was slightly though significantly higher for cytotechnologists (57.0%) compared with pathologists (53.4%), adjusted for experience (P = .004); cervical cytology percentage effort (P = .0005); or cervical accession volume (P = .0002). Compared with the TBS panel, exact agreement was achieved for 55.1% of image ratings compared with 82.3% agreement at the level of Negative vs non-Negative for images with a single-panel interpretation. Agreement with the panel was highest for images classified as Low-Grade Squamous Intraepithelial Lesion and lowest for Atypical Squamous Cells qualified as either of Undetermined Significance or Cannot Exclude a High-Grade Squamous Intraepithelial Lesion. Reviewers were less sensitive in identifying high-grade glandular lesions than they were in identifying high-grade squamous lesions at any threshold (P < .001). CONCLUSIONS: Morphologic appearances of images were more important determinants than participants' academic or professional degrees with regard to interobserver reproducibility in classifying cervical cytology images. Experienced cytotechnologists and pathologists performed similarly. Participants achieved higher sensitivity for identifying high-grade squamous lesions than they did for high-grade glandular lesions. These findings demonstrated that web-based studies may be useful in assessing interobserver agreement in classifying images.

Adenocarcinoma↗
PubMed2007

Parathyroid cyst: often mistaken for a thyroid cyst.

INTRODUCTION: Parathyroid cysts are rare but clinically significant lesions. They can be functional, mistaken for a thyroid cyst, and/or managed nonoperatively on occasion. METHODS: We identified seven patients (1 male, 6 females) with the diagnosis of parathyroid cyst from 1998 to 2003. RESULTS: Altogether, 33% of the patients had functional cysts. Sestamibi scans were performed in three of the seven patients, including two with functional cysts; none showed focal uptake. In toto, six of the seven cysts (86%) were found in an inferior parathyroid gland. All of the cysts had crystal-clear aspirate. C-terminal parathormone (PTH) levels were obtained from the aspirate from five of the seven (71%) patients. The mean level was 269,736 pg/ml (1970-1,268,074 pg/ml). Surgery was performed in three of the seven (43%) patients. All patients who underwent surgery improved postoperatively based on symptoms and serum levels of calcium and PTH. The four patients (57%) who were treated nonoperatively were subjected to aspiration alone; three (75%) of those patients required multiple aspirations. CONCLUSIONS: Most parathyroid cysts are nonfunctional and are rarely symptomatic. They are usually located in an inferior gland. If aspirated, most of the cysts reaccumulate fluid. Operative management is usually straightforward and alleviates symptoms and any biochemical abnormalities caused by the cyst.

Adult↗
PubMed2006

Quantitative multiplex methylation-specific PCR analysis doubles detection of tumor cells in breast ductal fluid.

PURPOSE: The challenges of cytology for accurate diagnosis of breast cancer are well recognized. We previously showed that normal and tumor tissue can be distinguished using a technique called quantitative multiplex methylation-specific PCR (QM-MSP). We hypothesized that quantitative analysis of methylated genes will provide enhanced detection of cancer cells present in cytologic specimens. EXPERIMENTAL DESIGN: QM-MSP was done on ductal lavage cells from a set of 37 ductal lavage samples from women undergoing mastectomy (27 with cancer and 3 without). Duct histology information was available for each lavaged duct. QM-MSP data was assessed by measuring cumulative methylation index and by receiver operating characteristic threshold analysis. To determine the baseline level of methylation for each gene in this population, cells from 60 ducts of women at high risk of developing breast cancer were analyzed. RESULTS: QM-MSP findings on a panel of nine genes were correlated to duct histology and ductal lavage cytology. Cytology detected cancer in 33% (7 of 21 ducts) with a specificity of 99% (92 of 93). QM-MSP detected cancer as calculated by cumulative methylation index with a sensitivity of 62% (13 of 21) and specificity of 82% (62 of 76) and by receiver operating characteristic threshold analysis with a sensitivity of 71% (15 of 21) and specificity of 83% (63 of 76). CONCLUSIONS: Compared with cytology, QM-MSP doubled the sensitivity of detection of cancer. This study provides proof of principle by showing the advantages of using methylation analyses to query cytologic specimens and indicates its potential use in diagnosis and in stratifying risk.

Body Fluids↗
PubMed2006

Birt-Hogg-Dubé syndrome: clinicopathologic findings and genetic alterations.

CONTEXT: Birt-Hogg-Dubé (BHD) syndrome is a rare clinicopathologic condition transmitted in an autosomal dominant fashion. This complex entity is characterized by cutaneous fibrofolliculomas, kidney tumors, pulmonary cysts, and spontaneous pneumothorax. Recently, the gene possibly responsible for the clinical manifestations of BHD syndrome has been cloned and characterized. The few reviews of BHD syndrome found in the English literature mostly focus on the skin lesions or genetics, with limited information on other pathologic changes, particularly the kidney lesions. OBJECTIVE: To review the literature on this subject with a special emphasis on BHD syndrome-associated renal pathology as well as recent advances in molecular genetic discovery of the BHD syndrome. DATA SOURCES: We used all data available after performing a literature search using MEDLINE and searching under the headings "Birt-Hogg-Dubé," "hybrid oncocytic tumors," and "folliculin." CONCLUSIONS: The presence of BHD syndrome should be investigated in any patient with multiple bilateral kidney tumors, especially if the predominant histologic type is chromophobe renal cell carcinoma or the so-called hybrid oncocytic tumor. The genetic alteration for BHD syndrome has been mapped to chromosome 17p12q11, and the gene in this region has been cloned and believed to be responsible for the BHD syndrome. The function of the BHD product, called folliculin, is still unknown, although it is speculated to be a tumor suppressor gene. Numerous mutations have been described in the BHD gene. Studies are ongoing to determine the relationship between the BHD gene and development of sporadic renal cell carcinoma and other lesions.

Carcinoma, Renal Cell↗
PubMed2005

Ductal lavage findings in women with mammographic microcalcifications undergoing biopsy.

BACKGROUND: We designed a prospective study to assess the likelihood that early lesions presenting as mammographic calcifications could be accessed for cytological diagnosis by ductal lavage (DL). METHODS: Consenting women with calcifications (Breast Imaging Reporting and Data System 4 or 5) underwent DL of fluid-yielding ducts (FYDs) before stereotactic core or excisional biopsy. The DL catheter was used to inject .2 to 1 mL of Isovue 300 into the duct to determine whether the FYD corresponded to the duct containing calcifications (designated overlap). Additional FYDs were injected, if possible, until overlap was identified. DL cytology was compared with histology. RESULTS: Twenty women were enrolled (mean age, 54.2 years); the mean size of the calcification-bearing area was 190 mm(2). The histological findings were as follows: 1 invasive cancer, 9 ductal carcinomas-in-situ (DCIS), 5 atypical hyperplasias, and 5 usual hyperplasias or fibrocystic changes. Four women had no FYD. In 15 women who underwent DL and ductography, overlap of dye and calcifications was seen in 4 (27%): 1 fibrocystic change, 1 hyperplasia, 1 atypical hyperplasia (cytological diagnosis mildly atypical), and 1 DCIS (cytological diagnosis benign). Of the remaining 8 DCIS lesions, 4 had no nipple aspiration fluid, 1 showed extravasation, and 3 were lavaged but the duct did not overlap. CONCLUSIONS: These results are consistent with data from women undergoing mastectomy for larger invasive cancer and DCIS and show that cancer-containing ducts do not yield nipple fluid in most cases.

Biopsy↗
PubMed2005

A comparison of ductoscopy-guided and conventional surgical excision in women with spontaneous nipple discharge.

INTRODUCTION: Radiologic imaging is routinely used to evaluate women with spontaneous nipple discharge (SND), but definitive diagnosis is usually only achieved by surgical terminal duct excision (TDE). Ductoscopy has been reported to result in improved localization of intraductal lesions and may avoid surgery in women with endoscopically normal ducts. MATERIALS AND METHODS: We conducted a retrospective review of the records of 117 consecutive women who underwent ductoscopy to guide ductal excision (scope-DE) or received conventional TDE without ductoscopy. Two women had atypical ductal lavage cytology and the remainder presented with SND from 1 or more duct. Preoperative evaluation included radiologic imaging as clinically indicated. RESULTS: Fifty-nine women underwent scope-DE, and 58 underwent conventional TDE. There were no significant differences in age, race, discharge characteristics, or radiologic findings. The proportion of women with intraductal neoplasia was slightly greater in the group undergoing scope-DE (88% vs. 81%, P = 0.2). In the conventional TDE group, 8.5% were found to have atypical hyperplasia or duct carcinoma in situ compared with 18.6% in the scope-DE group. In the ductoscopy group, 22 of 59 (37.3%) had lesions >5 cm from the nipple, compared with 1 of 17 women for whom distance of the lesion from the nipple was known in the conventional group (P = 0.02). Of the ductoscopy-detected cancers, 5 of 6 had no symptoms other than SND, whereas 1 of the 4 malignancies in the conventional group presented as SND alone. DISCUSSIONS: Ductoscopy identifies intraductal lesions in a high proportion of women with SND, and it may contribute to more accurate resection of these. A prospective study is required to obtain an unbiased assessment of these possible advantages.

Adult↗
PubMed2005

Endocrine biomarkers in ductal lavage samples from women at high risk for breast cancer.

BACKGROUND: Ductal lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of ductal lavage in this setting. METHODS: Tamoxifen-eligible, high-risk women underwent ductal lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) alpha, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The ductal lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF). RESULTS: One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low (P for interaction = 0.001). CONCLUSIONS: Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.

Biomarkers, Tumor↗
PubMed2004

Microcystic adenoma of the pancreas: clinical, radiologic, and cytologic features.

BACKGROUND: Cytology literature on pancreatic microcystic adenoma is sparse. It is important to separate microcystic adenoma from adenocarcinoma and mucinous cystic neoplasms on aspiration cytology, because patients with microcystic adenoma can be treated conservatively unless they are symptomatic. Potential pitfalls with endoscopic ultrasound (EUS) sampling of these lesions is discussed. METHODS: From January 1991 through June 2003, 10 patients with microcystic adenoma of the pancreas were diagnosed on fine-needle aspiration cytology. An additional patient, who was diagnosed with a mucinous cystic neoplasm by EUS sampling, was rediagnosed with microcystic adenoma on the excised specimen. Aspirate smears, cell blocks, core biopsies, subsequent excision (if any), and special stains were reviewed. Imaging studies and clinical data were available from the majority of patients. RESULTS CLINICAL RESULTS: The patients included 5 females and 6 males who ranged in age from 45 years to 84 years. Radiology studies showed tumors, which were heterogeneous with areas of fluid density and septations, located in the head, body, or tail of the pancreas. The masses ranged in size from 1 cm to 17 cm. The radiographic impression was highly suggestive of microcystic adenoma in six patients; detailed radiologic information was not available from three patients. On follow-up, six patients were alive and well at the last follow-up available, two patients died of unrelated sepsis, and three patients were lost to follow-up. Three of 11 patients underwent a Whipple resection. Cytology results: The cytologic features identified included the following: 1) Bland tumor cells were seen in sheets or small groups with a lack of nuclear abnormalities and moderate-to-scant cytoplasm with occasional clearing or vacuolation. Naked nuclei were present occasionally. Tumor cells were distinguishable from acinar cells based on larger cell size and granular cytoplasm in which prominent nucleoli were seen. 2) Relatively acellular, fibrovascular stroma was seen, usually located between tumor cells. 3) Calcifications were seen in four of eleven tumors. One tumor sampled by EUS revealed fragments of glandular-type epithelium with minimal atypia and was diagnosed erroneously as a mucinous cystic neoplasm. Cell blocks or core biopsies from most tumors showed fragments of dense stroma and cystic spaces lined by flattened epithelial cells. Subsequent Whipple resection in three patients showed histologic features of microcystic adenoma. Special stains performed in select tumors were positive for cytokeratin, carbohydrate antigen 19.9, and periodic acid-Schiff stain. Calretinin staining was negative in the tumor cells. CONCLUSIONS: A cytologic diagnosis of microcystic adenoma is possible based on the criteria described above. Cell block and/or core biopsy, special stains, and radiologic information are key in making a definitive diagnosis. Patients with microcystic adenoma are spared a major surgical procedure unless they are symptomatic. With the EUS-guided modality of pancreatic sampling, caution should be exercised in misinterpreting benign glandular epithelium derived from the stomach or small bowel as a mucinous cystic neoplasm.

Adenoma↗
PubMed2004

Second edition of 'The Bethesda System for reporting cervical cytology' - atlas, website, and Bethesda interobserver reproducibility project.

A joint task force of the American Society of Cytopathology (ASC) and the National Cancer Institute (NCI) recently completed a 2-year effort to revise the Bethesda System "blue book" atlas and develop a complementary web-based collection of cervical cytology images. The web-based collection of images is housed on the ASC website, which went live on November 5th, 2003; it can be directly accessed at http://www.cytopathology.org/NIH/.

Journal Article↗
PubMed2004

Ductal lavage findings in women with known breast cancer undergoing mastectomy.

BACKGROUND: Ductal lavage has the potential to detect cancer by sampling breast epithelium in asymptomatic high-risk women. To assess the utility of ductal lavage as a cancer diagnostic test, we investigated the association between ductal lavage cytologic findings and histologic findings in women with known breast cancer undergoing mastectomy. METHODS: Ductal lavage was performed in the operating room before mastectomy on 44 breasts from 32 women with known cancer and on eight breasts from seven women undergoing prophylactic mastectomy, two with occult malignancy. If the ductal lavage sample from one or more ducts contained enough epithelial cells for a cytologic diagnosis, lavaged ducts were injected with a mixture of colored dye, gelatin, and a radiographic contrast compound after mastectomy, and breast tissue was radiographed and sectioned. Histologic findings in ducts with and without dye were recorded. Associations between cytologic results and histologic results were examined by univariate and multivariable analyses. RESULTS: At least one duct was lavaged in 36 breasts (mean = 1.4 ducts per breast); all histologic and cytologic procedures were completed in 28 breasts and in 39 ducts. Markedly atypical or malignant cytology was found in five cancer-containing breasts. In 39 ducts with complete cytologic and histologic data and when marked atypia or malignant cells defined a positive cytologic test, sensitivity was 43% (95% confidence interval [CI] = 23% to 72%), specificity was 96% (95% CI = 86% to 100%), and accuracy was 77% (95% CI = 63% to 89%). When mild or marked atypia or malignant cells defined a positive cytologic test, sensitivity was 79% (95% CI = 57% to 96%), specificity was 64% (95% CI = 46% to 83%), and accuracy was 69% (95% CI = 55% to 83%). When all 31 cytologically evaluable breasts were analyzed, sensitivity was 17% (95% CI = 7% to 35%), specificity was 100% (95% CI = 5% to 100%), and accuracy was 19% (95% CI = 9% to 38%). CONCLUSION: In breasts with cancer, ductal lavage appears to have low sensitivity and high specificity for cancer detection, possibly because cancer-containing ducts fail to yield fluid or have benign or mildly atypical cytology.

Adult↗
PubMed2003

Atypical squamous cells: update on current concepts.

Besides all the confusion and associated problems that the use of ASC has created, it has initiated substantial investigational interest that has resulted in a better understanding of squamous intraepithelial lesions and the biology of cervical neoplasia. Although the category of ASC has created, and will continue to create, controversy in the diagnostic and management fields, it allows the pathologist to convey uncertainty that may be the result of poor sampling or difficulty in interpretation of a case. It is a valuable tool that the cytopathologist can use to make it known that the Papanicolaou test has its limitations and may need and benefit, in some instances, from support from ancillary studies. Similar limitations are recognized in other areas of pathology and the use of immunohistochemistry or molecular studies is widely accepted as an aid to a more specific and definitive interpretation. The time for the Papanicolaou test to be considered similarly has arrived. HPV DNA testing may not be the perfect test for cervical cancer screening because of high prevalence of HPV infection in the general population; however, it is currently the best-studied ancillary test and has been proven to be cost-effective for the triage of Papanicolaou tests with equivocal squamous cells. It is important for the cytopathologist to have well-developed diagnostic skills in interpreting gynecologic preparations, and to classify cases as ASC only when deemed appropriate. Downgrading cytologic findings that are diagnostic of a squamous intraepithelial lesion to ASC with the hope of supporting it by an HPV test will only result in a devaluation of the Papanicolaou test. Such recourse may, however, be acceptable in specific situations, such as in patients who have complex histories, atypical clinical presentations, or during pregnancy. Quality assurance measures to closely monitor the ASC:SIL ratio and the rate of HPV positivity in ASC cases will be essential to ensure the appropriate use of this interpretive category. The coordination of the 2001 Bethesda and ASCCP consensus meetings resulted in the new subcategories of ASC-US and ASC-H, along with well-defined management strategies for these interpretations. This new and clinically relevant terminology should lead to a reduction in difficulties at the clinical level and a more uniform management of patients, unlike the situation following Bethesda 1991 where the gynecologist was faced with a new "diagnosis" without specific management recommendations. The standardization of reporting and clinical management will also allow more reliable evaluation of patient outcomes and cost analysis. The 2002 American Cancer Society guidelines did not make specific recommendations regarding HPV DNA testing for the triage of patients who have a cytology result of ASC-US [64]. The FDA approved the expanded use of HPV testing in conjunction with the Papanicolaou test for cervical cancer screening in March of 2003. The future is likely to bring additional testing modalities that may be more specific for detecting squamous lesions that are more likely to persist or progress to carcinoma, than the currently available HPV tests. In addition, looking to the more distant future, recently published data from HPV vaccine trials suggests that immunizing women who are negative for HPV-16 may eventually reduce the incidence of cervical cancer [65]. At the present, however, the most effective method to decrease the mortality of this disease process is to make sure that all women have access to, and receive, effective cervical cytologic screening.

Female↗
PubMed2002

Is preoperative investigation of the thyroid justified in patients undergoing parathyroidectomy for hyperparathyroidism?

BACKGROUND: The finding of coexisting nodular thyroid disease during neck exploration for hyperparathyroidism (HPT) is reported to range from 20%-60%. Thus, the surgeon may encounter a second, unrelated lesion during open parathyroidectomy. Furthermore, with the recent introduction of minimally invasive surgery for HPT, the entire neck may not be explored, and it is important to know the potential risk of missing significant, concurrent thyroid disease. The diagnosis and timely treatment of associated thyroid abnormalities is desirable because a delay in operating would result in increased morbidity associated with a second neck exploration. DESIGN: We examined our 25-year experience at a large tertiary academic medical center, to determine the incidence and type of concurrent thyroid disease seen in patients with HPT. The computerized records of the Department of Pathology, from 1974-1999, were reviewed for patients with primary HPT who underwent surgery. RESULTS: A review of records from 580 patients who underwent surgery for primary HPT showed 103 (18%) patients with concomitant thyroid disease at surgery. All 103 underwent thyroid resection at the time of parathyroidectomy. Thyroid histology showed: 12 (12%): well-differentiated papillary carcinomas, 31 (30%): follicular adenomas, 49 (48%): nodular hyperplasias, 8 (8%): chronic lymphocytic thyroiditis, 1 benign cyst, 1 metastasis, and 1 normal. CONCLUSIONS: Synchronous thyroid disease was found in 18% of primary HPT patients undergoing surgery, and 12% of thyroid lesions were malignant. The overall malignancy rate was 2%. All primary malignancies found were papillary carcinomas, of which 7 of 12 (58%) were microcarcinomas. The significant association of simultaneous pathology in the two glands justifies preoperative thyroid imaging and fine-needle aspiration (FNA) biopsy to determine the best surgical approach for patients with HPT.

Adenoma↗
PubMedDate not supplied

Cytologic and histologic findings in multiple renal hybrid oncocytic tumors in a patient with Birt-Hogg-Dubé syndrome: a case report.

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare autosomal dominant neoplastic syndrome characterized by multiple skin lesions, lung cysts and renal tumors. A variety of histologic types of renal tumors have been reported, including clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC, oncocytoma and a recently described hybrid oncocytic tumor, which is thought to be highly associated with BHD. CASE: We report a case of a 48-year-old woman with BHD who initially presented to our institution with spontaneous pneumothorax and was found to have multiple lung cysts and renal tumors on computed tomography. We describe the fine needle aspiration findings of one of the renal tumors, which was suggestive of so-called hybrid oncocytic tumor. We also describe the gross and histologic findings of the multiple kidney tumors that the patient subsequently had excised. CONCLUSION: When multiple kidney tumors from a single patient appear oncycytic on fine needle aspiration, especially when focal clear cells are present, the possibility of oncocytomas and hybrid tumors associated with BHD must be entertained.

Adenoma, Oxyphilic↗