Maria A. Friedlander

Suitability of Thoracic Cytology for New Therapeutic Paradigms in Non-small Cell Lung Carcinoma: High Accuracy of Tumor Subtyping and Feasibility of EGFR and KRAS Molecular Testing

Introduction: The two essential requirements for pathologic specimens in the era of personalized therapies for non-small cell lung carcinoma (NSCLC) are accurate subtyping as adenocarcinoma (ADC) versus squamous cell carcinoma (SqCC) and suitability for EGFR and KRAS molecular testing. The aim of this study was to comprehensively review the performance of cytologic specimens for the above two goals in a high-volume clinical practice. Methods: Subtyping of primary lung carcinomas by preoperative cytology was correlated with subsequent resection diagnoses during a 1-year period (n = 192). The contribution of various clinicopathologic parameters to subtyping accuracy and utilization of immunohistochemistry (IHC) for NSCLC subtyping were analyzed. In addition, the performance of cytologic specimens submitted for EGFR/KRAS molecular testing during a 1-year period (n = 128) was reviewed. Results: Of the 192 preoperative cytology diagnoses, tumor subtype was definitive versus favored versus unclassified in 169 (88%) versus 15 (8%) versus 8 (4%) cases, respectively. Overall accuracy of cytologic tumor subtyping (concordance with histology) was 93% and accuracy of definitive diagnoses 96%. For a group of patients with ADC and SqCC (n = 165), the rate of unclassified cytologic diagnoses was 3% and overall accuracy 96%. IHC was used for subtyping of 9% of those cases, yielding 100% accuracy. The strongest predictors of difficulty in subtyping of ADC and SqCC were poor differentiation (p = 0.0004), low specimen cellularity (p = 0.019), and squamous histology (p = 0.003). Of 128 cytologic specimens submitted for molecular testing, 126 (98%) were suitable for analysis, revealing EGFR and KRAS mutations in 31 (25%) and 25 (20%) cases, respectively. Conclusions: Cytologic subtyping of NSCLC is feasible and accurate, particularly when morphologic assessment is combined with IHC. Furthermore, routine cytologic specimens can be successfully used for EGFR/KRAS mutation analysis. Our data strongly support the suitability of cytologic specimens for the new therapeutic paradigms in NSCLC.

Anorectal cytology as a screening tool for anal squamous lesions: cytologic, anoscopic, and histologic correlation.

Anorectal cytology has been increasingly used as a screening method for anal squamous lesions, particularly in high‐risk, homosexual, patients with human immunodeficiency virus infection. The diagnostic cytologic, anoscopic, and histologic criteria bear some resemblance to the criteria used in cervicovaginal samples with few differences. It is important to recognize these differences because they can lead to an erroneous diagnosis of dysplasia and unnecessary procedures.

Diagnostic pitfalls in fine needle aspiration biopsy of the spleen

Fine needle aspiration (FNA) of the spleen is rarely performed, due to fear of procedure complications. The objective of this study is to review the cytologic diagnoses of aspiration biopsy of the spleen performed in a cancer center.

Fine needle aspiration biopsy of primary mucinous carcinoma of the skin: a case report.

BACKGROUND Primary mucinous carcinoma of the skin is a rare neoplasm of sweat gland origin. To date there are only 2 case reports in English describing its features on fine needle aspiration biopsy (FNAB). We describe an additional case and review the literature regarding this entity. To the best of our knowledge, this is the first reported case with a sentinel lymph node biopsy. CASE A 78-year-old woman presented with a 3-cm left scalp mass at an outside institution. Following incomplete excision, multiple subcentimeter nodules developed in the skin adjacent to the biopsy site. FNAB of the nodules confirmed a recurrence of mucinous carcinoma. Clinical examination and extensive radiographic studies did not reveal primary disease elsewhere, thus supporting a diagnosis of primary mucinous carcinoma of the skin. At the time of wide excision of the residual tumor, sentinel lymph node biopsy revealed a single focus of micrometastasis. The patient declined adjuvant therapy and was disease free 6 months after the initial diagnosis. CONCLUSION Cutaneous mucinous carcinoma is a tumor characterized by bland histocytologic features and abundant extracellular pools of mucin. Without a high index of suspicion, this rare entity may be overlooked or misdiagnosed. Numerous benign and malignant mucin-producing primary and secondary mimics exist, and immunohistochemistry offers limited benefits in differentiating them. Cytologic diagnosis of primary mucinous carcinoma of the skin is possible; however, correlation of clinical, radiologic and pathologic features is necessary to arrive at an accurate diagnosis.

Cytology workforce study: a report of current practices and trends in New York State.

A survey was conducted among 130 New York State (NYS) registered cytology laboratories to better understand current and future changes in the practice of cytology, changes in the cytotechnologist (CT) scope of practice, and the future need for CTs. A 51.5% (67/130) response rate was obtained. Trends for gynecologic case volume varied across facility types. Nongynecologic volume is growing primarily in hospitals and large medical center laboratories and private laboratories; the fine-needle aspiration volume is growing in hospital and large medical center laboratories. One third of responding laboratories anticipate a continued demand for CTs within the next 3 years owing to impending retirements. Few laboratories also report the gradual adoption of molecular testing with CTs directly involved. Because 60% (3/5) of NYS CT training programs have closed since 2008, the 2 remaining programs are a valuable key staffing resource for CTs. Continued viability of these programs is essential to provide the necessary training and staffing of NYS laboratories for cytopathology practice.

Novel Modification of HistoGel-Based Cell Block Preparation Method: Improved Sufficiency for Molecular Studies

CONTEXT - Cell block preparation methods vary substantially across institutions and are frequently suboptimal. The growing importance of biomarker testing in the era of targeted therapies makes optimization of cell block preparation critically important. OBJECTIVE - To develop an improved cell block preparation method. DESIGN - Ex vivo fine-needle aspirates and scrapes from surgically resected tumors were used to develop an improved HistoGel (Thermo Fisher Scientific, Waltham, Massachusetts)-based cell block preparation method. Cellularity yield with the new versus the standard method was assessed in ex vivo split samples and in consecutive clinical fine-needle aspirates processed before (n = 100) and after (n = 100) the new method was implemented in our laboratory. Sufficiency of cell block material for potential molecular studies was estimated by manual cell quantitation. RESULTS - The key modification in the new method was pretreatment of the pelleted cells with 95% ethanol before the addition of HistoGel (HistoGel + ethanol method). In addition, we optimized the melting conditions of HistoGel and added a dark, inorganic marker to the cell pellets to highlight the desired level of sectioning during microtomy. Cell blocks from ex vivo split samples showed that the HistoGel + ethanol method yielded, on average, an 8.3-fold (range, 1-20) greater cellularity compared with the standard HistoGel-only method. After the switch from the standard HistoGel method to the modified method in our clinical practice, sufficiency of positive fine-needle aspirates for some molecular studies increased from 72% to 97% ( P = .002). CONCLUSIONS - We describe a simple and readily adoptable modification of the HistoGel method, which results in substantial improvement in cell capture in cell blocks, leading to a significant increase in sufficiency for potential molecular and other ancillary studies.

Cytologic assessment of estrogen receptor, progesterone receptor, and HER2 status in metastatic breast carcinoma

BACKGROUND Discordance in the receptor status between primary breast carcinomas (PBC) and corresponding metastasis is well documented. Interrogation of the receptor status of metastatic breast carcinoma (MBC) in cytology material is common practice; however, its utility has not been thoroughly validated. We studied patients with MBC, and evaluated the concordance rates of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between PBC surgical specimens and corresponding MBC cell blocks (CBs). We correlated the findings with clinicopathologic variables and with the fixation methods used. METHODS We searched for patients with MBC diagnosed on cytology from 2007 to 2009 and selected those with ER, PR and HER2 tested in both the PBC surgical specimens and the MBC CBs. We included CBs fixed in formalin and methanol based solution (CytoLyt®). All slides were reevaluated by cytopathologists. Clinical information was retrieved from the medical records. RESULTS We studied 65 patients with PBC and MBC paired specimens. The concordance rates between PBC and MBC were 78.5%, 58.5% and 96.9%, for ER, PR and HER2, respectively. When discordant, PR status switched from positive (PBC) to negative (MBC) in most cases (23/27). The PR concordance rate was 45.2% for CBs fixed in formalin and 70.6% for those fixed with CytoLyt® (p=0.047). CONCLUSION The ER, PR and HER2 concordance rates between the PBC and MBC CBs are similar to those reported in paired surgical specimens. PR status was the most prevalent discordance and was not accompanied by a switch in ER.

My Career Path Story: From Cytotechnologist to Regulatory Manager

and 6 performing circulating tumor cell analysis. Currently there are also 6 CTs who perform no routine cytology activities, whereas in the past all CTs performed routine cytology. In conclusion, I believe that the field of Cytology is still full of very exciting opportunities; however, it is important to keep an open mind and embrace change and new ideas as they present themselves. In order to remain relevant, it is also important to continually work to develop and improve our skills. Concerns for the future of Cytology include the loss of Cytotechnology Programs as the field has evolved – Programs will need to evolve to meet the needs of this changing profession.

Personnel Licensure Updates: California, New York and Washington D.C.

Across the country, the beginning of a new year brings with it new legislative proposals for potential consideration. Since the beginning of this year, there has been licensure related activity in California, New York and Washington D.C., as summarized below. It is important for cytotechnologists and pathologists to be vigilant concerning licensurerelated activities in our community. The stringency of state licensure laws can negatively impact scope of practice and recruitment of highly qualified cytotechnologists. The licensure law of one state can also potentially affect laboratories located in other states as is described below in New York. The American Society of Cytopathology (ASC) has published Guidelines and Resources for Cytotechnologist State Licensure and encourages its members to urge state legislatures to consider these guidelines as model language to describe the qualifications and scope of practice of cytotechnologists.1