Mujtaba Husain

Multicenter masked evaluation of AutoCyte PREP thin layers with matched conventional smears. Including initial biopsy results.

OBJECTIVE To compare the performance of liquid-based cell preparations from the AutoCyte PREP system (AutoCyte, Inc., Elon College, North Carolina) with the conventional cervical smear in masked, split-sample, multisite trials. STUDY DESIGN The AutoCyte PREP system utilizes the CytoRich method, which combines liquid preservation, selective reduction of blood and inflammation, thin-layer cell dispersion and discrete staining. In an eight-site multicenter trial, 8,983 cases were evaluated. Parallel AutoCyte PREP slides and matching conventional cervical cytologic smears were screened in a masked fashion, with all abnormals reviewed in a masked, on-site pathologist review. The conventional smear was always prepared first, with the AutoCyte PREP using the residual cells on the collection device. The Bethesda System was used for reporting diagnosis and specimen adequacy. RESULTS Of the cases, 7,805 (86.9%) had the same interpretation. In 8,750 cases (97.4%), there was agreement within one diagnostic category. The AutoCyte PREP demonstrated a statistically significant, 31% overall improvement in the detection of squamous intraepithelial lesion and invasive cancer when evaluating cases with more than one diagnostic class difference. Biopsy correlation of available data supported the improvement observed in the cytology-based comparison. Recovery of infectious organisms and endocervical component was comparable between preparations, especially in light of the split-sample study design. There was a 39% reduction in unsatisfactory slides and 44% fewer satisfactory but limited by reports. CONCLUSION The AutoCyte PREP and CytoRich method produce excellent cellular presentations with standardized quality, superior sensitivity and improved adequacy as compared to the conventional method.

T-cell lymphomas of large cell type. A variety of malignant lymphomas: "histiocytic" and mixed lymphocytic-"histiocytic".

Clinical and morphologic features of seven T‐cell lymphomas of the large cell type are described. The tumors were grouped into those with irregular (3 cases) and those with round and regular nuclei (4 cases). In both groups, variation in cell size, numerous histiocytes and vessels, and many mitoses were distinguishing features. In only 1 case in the round and regular nucleus group was there relatively little variation in cell size and a paucity of histiocytes. Abundant polyribosomes, long strands of rough endoplasmic reticulum, and lysosomal granules were prominent electron microscopic features in both groups of tumors. The clinkal presentations and courses varied considerably, especially in patients with tumors of the round nucleus type. One patient presented initially with chronic lymphocytk leukemia, 1 with Lennerts lymphoma, another with bone marrow infiltration, and a fourth with subcutaneous tumors. Two patients with the round nucleus type are still alive one and a half and two years after the original diagnosis. Two patients died two years after the onset of symptoms. Each of the 3 patients with tumors of the irregular nucleus type had a rapid clinical course and died within ten months. Cancer 46:87–101, 1980.

Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women

While infection with high‐risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV‐16 DNA‐positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT‐PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV‐16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20–7.76), smoking (OR = 3.0, 95% CI 1.19–7.56), high viral load (OR = 5.27, 95% CI 2.05–13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1–47.58) and high transcript copies (OR = 5.56, 95% CI 2.05–13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV‐16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV‐16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

Endometrial ablation by hysteroscopic instillation of hot saline solution

Current methods of endometrial ablation to treat excessive uterine bleeding use laser or electrosurgical energy sources. These procedures are highly skill dependent, and numerous cases of fluid overload as well as other complications have been reported. A new method of endometrial ablation instills heated 0.9% normal saline at 80 to 90 degrees C. The fluid is recirculated and therefore, it is possible to measure accurately and predetermine the maximum amount of allowable absorption that occurs. Animal data indicate that the procedure is effective and may be safer than current methods of endometrial ablation. Standardization of this new method will require clinical trials, initially with women undergoing hysterectomy, for proper evaluation of the extent of thermal damage in relation to the time and intensity of heat exposure.

Cervical cytology specimen adequacy: Patient management guidelines and optimizing specimen collection

Objective. To provide updated management guidelines according to cervical cytology specimen adequacy and techniques to optimize adequacy based on literature review and expert opinion. Materials and Methods. Selected members of the American Society for Colposcopy and Cervical Pathology committee and invited experts conducted a literature review and discussed appropriate management and areas for future research emphasis. Results. The guidelines recommend a repeat Pap test in a short interval of 2 to 4 months for most women when the cytology result is unsatisfactory. The preferred follow-up for women with a negative cytology result lacking an endocervical/transformation zone component or showing other quality indicators is a repeat Pap test in 12 months. Indications for an early repeat Pap test in 6 months are provided, and the influence of human papillomavirus testing results on management is discussed. Techniques for optimizing specimen adequacy are provided in detail. Conclusion. The specimen adequacy management guidelines will help promote uniform and optimal follow-up of patients receiving cervical cytology screening. The topics for future research emphasis will be helpful in promoting studies in needed areas.

Cytodiagnosis of benign and malignant hürthle cell lesions of the thyroid by fine-needle aspiration biopsy

Eighty‐two Hürthle cell (HC) lesions of the thyroid with cytologic evaluation by fine‐needle aspiration biopsy (FNAB) were reviewed. In 17 cases the FNAB was not diagnostic because the fine‐needle aspirates (FNAs) were too scanty in cellularity. Among the remaining 65 lesions, there were 45 HC adenomas (HCAs), six non‐neoplastic HC nodules (NHCNs), 10 primary HC carcinomas (HCCs), and four metastatic HCCs. Forty‐four HCAs were diagnosed as HC tumor (HCT), and one HCA was wrongly diagnosed as medullary carcinoma. All six NHCNs were wrongly diagnosed as HCT. Of 10 primary HCCs, three were diagnosed as HCT and seven as suspected HCC. Four metastatic HCCs were correctly diagnosed. The FNAs from 38 HCAs and four NHCNs were predominantly composed of large monomorphic HCs with oval nuclei, inconspicuous nucleoli, and abundant, well‐defined, granular cytoplasm present singly, in acinar arrangement, and in monolayered sheets of variable sizes. Nuclear pleomorphism and prominent nucleoli were noted in seven HCAs and two NHCNs. Occasional small syncytial tumor cell clusters (STCCs) were noted in six cases, and a few naked tumor cell nuclei (NTCN) were observed in 16 cases. The FNAs from 14 HCCs were hypercellular. In all cases tumor cells were relatively small and showed monomorphic or pleomorphic nuclei, prominent nucleoli, and ill‐defined cytoplasm. STCCs of variable sizes were present in abundance in 10 cases, and numerous NTCN were noted in 12 cases. In two HCCs, the tumor cells with well‐defined cytoplasm were present singly and in cohesive sheets, and no STCCs or NTCN were observed. Thus, the presence of small tumor cells with ill‐defined cytoplasm and prominent nucleoli in syncytial clusters and abundant NTCN in the FNA of a thyroid nodule should alert the observer about the strong possibility of an HCC. Diagn. Cytopathol. 1999;20:261–265. 

Combination of MUC5ac and WT‐1 immunohistochemistry is useful in distinguishing pancreatic ductal carcinoma from ovarian serous carcinoma in effusion cytology

Malignant ascites may be the first presentation of an unsuspected cancer. Pancreas and ovary are among the organs that are usually evaluated as a source of primary. The purpose of this study is to investigate a panel of immunohistochemical stains to help differentiate pancreatic from ovarian carcinoma. We evaluated the immunohistochemical staining of eight commercially available antibodies MUC1, MUC2, MUC5ac, Wilms tumor susceptibility gene 1 (WT1), cytokeratin 7 (CK7), CK20, CA125, and CA19.9 in 25 effusion specimens with evidence of metastatic carcinoma including 14 ovarian serous carcinomas, 9 pancreatic adenocarcinomas, and 2 unknown primaries. Primary ovarian serous carcinomas were positive for WT‐1 (100%), CK7 (93%), CK20 (43%), CA125 (100%), CA19.9 (50%), MUC1 (100%), MUC2 (0%), and MUC5ac (0%). Primary pancreatic carcinomas were positive for MUC5ac (100%), MUC1 (100%), CA19.9 (100%), CK7 (78%), CK20 (22%), CA125 (89%), WT‐1 (0%), and MUC 2 (0%). The combination of MUC5ac positivity/WT‐1 negativity was seen in 100% of pancreatic carcinoma, whereas MUC5ac negativity/WT‐1 positivity in 100% of ovarian serous carcinoma. It appears that the combination of MUC5ac and WT‐1 stains is useful in distinguishing pancreatic ductal from ovarian serous carcinoma in body fluid cytology. Diagn. Cytopathol. 2010.

Age-appropriate use of human papillomavirus vaccines in the U.S.

Cervical infections by approximately 15 cancer-associated (carcinogenic) human papillomavirus (HPV) genotypes cause virtually all cervical cancer and its immediate precursor lesions worldwide. Prophylactic vaccines against human papillomavirus (HPV) types HPV16 and HP18, which cause 70% of cervical cancer worldwide, hold great promise for reducing the burden of cervical cancer worldwide. However, current HPV vaccines prevent future infections and related cervical abnormalities and do not treat pre-existing HPV infections. In the U.S., HPV vaccine introduction should be considered in the context of a very successful cervical cancer screening program that has reduced the rates of cervical cancer by 75% or more. Thus, HPV vaccines will only prevent an incremental number of additional cervical cancers in the U.S. The introduction of HPV vaccines can also prevent other HPV-related sequelae, most importantly cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3), which precede the development of cervical cancer and require clinical follow-up and treatment. Examining data from 7 clinical centers in the U.S., the median age of CIN2/3 is typically between 25 and 30 years of age in 2007; if screen-detected CIN2/3 develops on average 5-10 years after the causal infection is acquired, HPV vaccination will only prevent a significant proportion of CIN2/3 if it is given to women before the age of 26 and more so if given to women 18 and younger. It is increasingly evident that prophylactic HPV vaccines will provide the greatest public health or population benefit only when delivered to adolescent, mostly HPV-naive women.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion: review of ancillary testing modalities and implications for follow-up.

Objective: To review the cytology category atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H), with human papillomavirus (HPV) and other ancillary testing results and according to age group. Methods: A literature search was performed on the ASC-H category, and studies analyzing ASC-H according to ancillary testing modalities or patient age groups during the past 4 years were emphasized. Results: The ASC-H category accounts for less than 1% of cytology reports, and 33% to 84% will test positive for oncogenic HPV. The number of patients with cervical intraepithelial neoplasia 2/3 and cancer on biopsy is quite variable, from about 12% to more than 70%, averaging about 40%. The variation reflects patient population as well as local laboratory practices, but older subgroups are more likely to have negative HPV results and negative follow-up. Both the sensitivity of HPV testing for cervical intraepithelial neoplasia 2/3 detection and the negative predictive value for a patient with ASC-H and negative HPV testing average more than 95%. Additional studies evaluating other types of ancillary testing for the ASC-H category are needed. Conclusions: Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, is an uncommon cytology result, and HPV testing results and biopsy follow-up show variation according to patient age group and local laboratory practices. A negative HPV result in ASC-H offers a high negative predictive value and could be considered as a management strategy in mature women as well as women 30 years and older receiving combined cytology and HPV screening.

Histopathologic and cytopathologic diagnostic discrepancies in head and neck region: pitfalls, causes, and preventive strategies.

BACKGROUND: Clinicians commonly utilize fine needle aspiration biopsy (FNAB) for the primary investigation of head and neck masses. Correlation of these results with the surgical resection diagnosis is an essential part of quality control and assurance programs in all cytology laboratories. METHODS: Of 610 cases, 20 (3.3%) had corresponding surgical resections performed within 3 months of the FNAB, with a discrepant diagnosis identified through a search that involved all FNABs performed on the head and neck region, excluding the thyroid gland, at Wayne State University between 1999 and 2004. Sites of discrepant samples included the parotid or submandibular gland (n = 5), lymph nodes (n = 8), and paratracheal/paraesophageal neck masses (n = 7). RESULTS: The reasons of false-negative FNABs included sampling errors (n = 3), insufficient material for an adequate interpretation (n = 5), lack of triage necessary for ancillary studies (n = 4), and interpretation errors (n = 6). There were 2 false-positive FNABs, both reported as mucoepidermoid carcinoma and showed chronic sialadenitis in one and lymphoepithelial cyst in the other. CONCLUSIONS: FNAB is an effective tool for the diagnosis and triage of patients with head and neck masses that can be further improved with an onsite immediate adequacy evaluation and triage performed by a pathologist.