Shahla Masood

Interobserver variability in the classification of proliferative breast lesions by fine-needle aspiration: results of the Papanicolaou Society of Cytopathology Study.

This study evaluates the applicability of the published cytologic criteria in the categorization of proliferative breast lesions by assessing the diagnostic accuracy and interobserver reproducibility of a panel of experts. Twelve breast fine‐needle aspiration (FNA) specimens of biopsy‐proven nonproliferative breast lesion (NPL) (1 case), proliferative lesions without atypia (PL) (7 cases), proliferative lesion with atypia (PLA) (1 case), and low‐nuclear grade ductal carcinoma in situ (DCIS) (3 cases) were selected. Six FNAs were Papanicolaou (PAP) and 6 were Diff‐Quik‐stained (DQ). Six expert cytopathologists classified the smears using a summary of published criteria as a guideline. All 6 participants rendered the same cytologic diagnosis in 2/12 (16%) cases. The agreement among the 6 raters was low (Kappa = 0.35). Cytohistologic correlation was achieved in 26/72 (36%) FNA diagnoses. The correlation of the PAP‐stained cases was better than the DQ: 17/36 (47%) PAP and 9/36 (25%) DQ correlated. Improving the correlation was achieved by amalgamation of NPL and PL into “low risk” and PLA and DCIS into “high risk” categories: 47/72 (65%) FNA diagnoses then correlated with histology [29/36 (81%) PAP and 18/36 (50%) DQ]. We conclude that the cytologic criteria of proliferative breast lesions need to be further defined and assessed. Consideration should be given to minimizing the number of diagnostic categories and adopting a terminology that has a direct effect on patient management. Diagn. Cytopathol. 1998;18:150–165.

Expression and prognostic significance of estrogen and progesterone receptors in adenocarcinoma of the uterine cervix. An immunocytochemical study

Background. Adenocarcinoma of the uterine cervix typically is an aggressive neoplasm with a propensity for early invasion and dissemination. Little data are available correlating histologic, histochemical, or immunocytochemical parameters with the biologic behavior of this neoplasm. Specifically, the implication of expression of estrogen and progesterone receptors in cervical adenocarcinoma is essentially undefined.

Fine‐needle aspiration biopsy of nonpalpable breast lesions

Recent advances in radiologic imaging have resulted in a better recognition of subtle radiologic abnormalities and earlier detection of breast carcinoma. This has resulted in better overall survival for patients with tumors less than 1 cm in size. However, the cost-effectiveness of screening mammography is still a matter of debate, as only up to one-third of radiologically suspicious lesions are found to be malignant. Thus, tissue biopsy is essential to substantiate the ultimate diagnosis. These surgical biopsies indeed represent a significant percentage of the individual cost of screening for lesions that are often benign. To reduce the number of unnecessary open biopsies for women with abnormal mammograms and benign breast disease, other alternatives, such as needle biopsy, have been introduced. These less invasive sampling alternatives, i.e., fine-needle aspiration biopsy (FNAB) or core biopsy, can expedite patient diagnosis and treatment and may reduce costs. There are, however, many unresolved issues surrounding the choice of the needle and the localizing device as well as the precise morphologic evaluation of nonpalpable breast lesions. When used in conjunction with appropriate radiologic guidance and by experienced hands, FNAB has improved the specificity of mammography. Similarly, the reported sensitivity and specificity of FNAB of nonpalpable breast lesions approximate the results obtained from FNAB of palpable breast lesions. Fine-needle aspiration biopsy of nonpalpable breast lesions, however, carries a significantly higher insufficiency rate than core biopsy. This limitation, coupled with advances in radiologic breast imaging, has contributed significantly to the current departure from FNAB and conversion to core biopsy. Today, except at a few oncology centers and academic institutions, occult breast lesions are being sampled by stereotaxic core biopsy procedures. These devices are rapidly being placed in academic institutions, cancer centers, the offices of radiologists, and, recently, in the offices of practicing surgeons. The use of stereotaxic biopsy is a financially viable marketing tool and is presented to many women as an attractive alternative to surgical biopsy. The level of complexity involved in the interpretation of a breast FNAB is different from that of core biopsy. FNAB requires the availability of an interested pathologist with special training in breast 197 CANCER CYTOPATHOLOGY

Cytomorphology of Fibrocystic Change, High-Risk, and Premalignant Breast Lesions

Abstract: Fine‐needle aspiration biopsy has proven to be an accurate and well‐tolerated procedure with a reported specificity of 99% and sensitivity of 70–99%. Similarly, nonpalpable breast lesions can be effectively sampled by needle biopsies under radiologic guidance. Breast aspirates have also been extensively utilized for assessment of nuclear grade, hormone receptor status, ploidy status, and proliferation rate, and have proven to be an attractive alternative to surgical biopsy. Using strict cytologic criteria, it may also be possible to recognize the cytomorphologic changes in breast lesions that are associated with increased risk for subsequent development of breast cancer. Presence of myoepithelial cells within the clusters of atypical epithelial cells recognized morphologically and/or detected by immunostaining for muscle specific actin is an important diagnostic feature of proliferative breast disease with atypia (atypical hyperplasia). This recognition has significant clinical implications and is important in the design of chemoprevention trials. The cytologic distinction between carcinoma in situ and invasive breast cancer remains difficult.

Is it time to retire the term of "in situ carcinoma" and use the term of "borderline breast disease?".

The article published in July 19, 2010 issue in the New York Times about a few patients who have undergone cancer therapy for over diagnosis of ductal carcinoma in situ (DCIS) brought international attention to this entity. The story of each patient was real and the message was powerful. The patients spoke about a serious issue that has had a major impact on their lives both emotionally and psychologically. Their stories brought to public attention an issue that has been known to the medical community for a long time. And yet we have no solutions to offer to resolve this issue. Several position papers from different societies were issued only to restore the trust of the public and to minimize the associated anxiety. Meanwhile discussions are taking place among the key opinion leaders and several organizations in an effort to explore some possibilities for future direction. The discipline of pathology is no different from other specialties in medicine in regard to differences in opinion and diversity in the pattern of practice. As in any other profession, mistakes are inevitable and often heavy prices are paid to compensate for the consequences. However, errors provide an opportunity for improvement. This is best reflected by the following statement made by Dr. John Azzopardi, an expert in Breast Pathology. ‘‘One relies on one’s experience. But ‘‘experience’’ can be merely the repetition of the same error often enough... One must be willing, even anxious, to learn from one’s error. This requires a degree of humility, a readiness to listen to the arguments of others, including those of one’s juniors, and the inclination to re-examine cases in which a mistaken diagnosis has been made and to analyse the reasons for the original mistake.’’ Distinction between atypical ductal hyperplasia (ADH) and low grade DCIS remains a diagnostic challenge in the everyday practice of breast pathology. Reported studies including a highly cited article by Dr. Rosai in 1991 continue to highlight the significant inter-observer variability even among experienced breast pathologists. This issue is compounded by the increasing number of tissue sampling by core needle biopsy as a consequence of screening mammography. The small sample size of core needle biopsies and tissue fragmentation contributes to the complexity of an accurate diagnosis of DCIS. It is important to recognize that assessment of core needle biopsy is different from circumstances under which the various diagnostic criteria were originally defined by reviewing multiple histologic sections obtained from surgical excisions. The real challenge is how to minimize the occurrence of over-diagnosis of DCIS and how to balance the scope of therapy based on the biology and the extent of this disease. Ductal carcinoma in situ is a heterogenous disease characterized by neoplastic proliferation of epithelial cells within a breast duct with no ability to metastasize. DCIS is considered a precursor lesion with a variable rate of progression into invasive breast cancer. Based on nuclear grade, presence or absence of necrosis and the pattern of morphologic features, DCIS is stratified into different grades and types. High nuclear grade lesions are associated with rapid growth and early progression to an invasive cancer and are easier to diagnose. In contrast, low nuclear grade lesions remain indolent and even when they progress to invasive cancer the tumor is frequently low grade and well differentiated. Low grade DCIS and high grade DCIS represent two genetically distinct entities that lead to different forms of invasive cancer. Low grade DCIS share similar morphologic and biologic features with ADH, which raises the question of whether these two lesions represent different spectrums of the same entity. Up to now, suggested terminologies of mammary intraepithelial neoplasia (MIN) by Dr. Rosai and ductal intraepithelial neoplasia (DIN) by Dr. Tavassoli have not been fully embraced by the pathology DOI: 10.1111/j.1524-4741.2010.01014.x

Recent Updates in Breast Fine-Needle Aspiration Biopsy

he history of the use of breast fine-needle aspiration T biopsy (FNAB) dates back to the 19th century. Martin and Ellis, (l), at the Memorial Hospital for Cancer and Allied Disease in New York, were the first to report their experience with this procedure in 1930. Since then, many other reports have appeared in the literature emphasizing the importance of FNAB in the evaluation of patients with breast lesions (2-5). However, the changes in the medical economy in the United States, and the emphasis on cost containment, have been a major factor in stimulating interest in the use of FNAB. Recognizing that the majority of breast lesions are benign and open biopsies are inconvenient and costly, FNAB is becoming an increasing cost-effective diagnostic tool in the assessment of breast lesions (6-8). Several studies (9-10) have focused on potential cost effective triage role of breast FNAB, that is, to stratify patients for a definitive biopsy performed in an outpatient setting under local anesthesia versus an inpatient setting using one-stage approach. The results of these studies have clearly shown the financial advantage of the use of FNAB as the initial approach to evaluate a patient with a breast lesion. Other advantages of FNAB include minimal physical and psychological discomfort to the patient. Fine-needle aspiration biopsy is a procedure that is easily accepted by a woman. This may lead to an earlier detection of

Nuclear grooves in fine‐needle aspiration biopsies of breast lesions: Do they have any significance?

Nuclear grooving is a recognized morphologic feature frequently seen in papillary carcinoma of the thyroid. This feature is also occasionally seen in other nonneoplastic and neoplastic conditions. Nuclear grooves have been described in tubular carcinoma of the breast. However, the significance of nuclear grooves in benign and malignant conditions of the breast has been rarely studied. In a retrospective study, we searched for the presence of nuclear grooves in Papanicolaou‐stained and Diff‐Quik‐stained fine‐needle aspiration biopsies (FNAB) of 50 cases of primary breast carcinoma, 25 cases of proliferative breast disease, and 25 cases of fibroadenoma. In addition, 10 cases of metastatic breast carcinoma diagnosed by FNAB were reviewed. Nuclear grooves were identified in 39 of 50 (78%) of the histologically confirmed primary breast carcinomas and in 9 of 10 (90%) of the cases of metastatic breast carcinoma in the Papanicolaou‐stained smears. Nineteen of 50 (38%) of the cases of proliferative breast disease/fibroadenoma showed nuclear grooves in the Papanicolaou‐stained smears. The difference between the percentage of cases showing nuclear grooves seen in the Papanicolaou‐stained primary breast carcinomas and metastatic breast carcinomas compared with the benign breast lesions was statistically significant (P < 0.001 in the primary breast carcinoma cases and P < 0.01 in the metastatic breast cancer cases). Nuclear grooves were identified less often in the Diff‐Quik‐stained smears, and their presence in malignant lesions versus cases diagnosed as benign breast disease was not statistically significant. This study suggests that, although the presence of nuclear grooves is more frequently seen in malignant breast lesions, their presence cannot totally exclude the possibility of benign breast disease. The presence of nuclear grooves, however, may serve as a diagnostic clue in metastatic tumors of unknown primary. Diagn. Cytopathol. 1998;18:333–337.

Prognostic Factors in Breast Cancer

Abstract: The overwhelming interest in breast cancer among researchers, clinicians, diagnosticians, and the public has resulted in an extensive search for better understanding and better control of the disease. The use of traditional, as well as the newly recognized, prognostic factors in breast cancer is an attempt to identify high‐risk breast lesions and administer a more aggressive therapeutic approach to minimize the possibility or progression of this disease. Herein the clinical significance of various prognostic factors are discussed and the need for a better standardized approach is emphasized.

Automation in cytology: a survey conducted by the New Technology Task Force, Papanicolaou Society of Cytopathology.

Despite the overwhelming interest in the development of several computer based technologies in the last several years, the role of automation in cytology has remained controversial. The potential of these technologies in the reduction of false negative results in pap smears is well recognized. However, there is still remarkable confusion as how to incorporate automation in the routine practice of cytology. This prompted the New Technology Task Force of the George Papanicolaou Society of Cytopathology to design a survey to seek the opinion of those engaged in cervicovaginal cytology screening regarding the value of automation in cytology.

A Plea for Standardization of Biomarker Assays in the Study of High Risk, Premalignant and Malignant Breast Disease

n the past few years, the field of cancer research has I greatly benefited from recent advances in cellular and molecular biology. Currently, newly recognized biomarkers are being examined as prognostic indicators to identify potentially aggressive tumors and to aid in planning appropriate treatment. A variety of tumor characteristics can provide prognostic information in patients with breast cancer. Although some of these characteristics are firmly established, others require large scale, controlled studies before they can be appropriately utilized. At the present time, no single marker is available that will predict which patient with primary breast cancer is destined to relapse, and controversy remains regarding the prognostic value of new markers (1). However, the availability of biological markers has provided us with an opportunity to understand the initial genetic events leading to the development of breast cancer. To control and ultimately to prevent breast cancer, we must identify the cascade of events that transforms a normal breast cell into a malignant cell. This may only be achieved through the precise knowledge of the complex alterations occurring at the cellular and molecular levels. Knowledge about these genetic events may eventually enable us to design prophylactic intervention, to discover additional biomarkers, to improve our ability to predict risk, and to enhance strategies for early detection. The goal of early detection efforts is to identify patients who will develop breast cancer. This task involves complex issues