One procedure-one report: the Re-Imagine Cytopathology Task Force position paper on small tissue biopsy triage in anatomic pathology.

INTRODUCTION: Endoscopic biopsy procedures increasingly generate multiple tissue samples from multiple sites, and frequently retrieve concurrent cytologic specimens and small core needle biopsies. There is currently lack of consensus in subspecialized practices as to whether cytopathologists or surgical pathologists should review such samples, and whether the pathology findings should be reported together or separately. MATERIALS AND METHODS: In December 2021, the American Society of Cytopathology convened the Re-Imagine Cytopathology Task Force to examine various workflows that would facilitate unified pathology reporting of concurrently obtained biopsies and improve clinical care. RESULTS AND CONCLUSIONS: This position paper summarizes the key points and highlights the advantages, challenges, and resources available to support the implementation of such workflows that result in "one procedure-one report".

The Performance of an Extended Next Generation Sequencing Panel Using Endobronchial Ultrasound-Guided Fine Needle Aspiration Samples in Non-Squamous Non-Small Cell Lung Cancer: A Pragmatic Study.

INTRODUCTION/BACKGROUND: Samples from endobronchial ultrasound-guided fine needle aspiration (EBUS-TBNA) are frequently used for next generation sequencing (NGS) in patients with non-small cell lung cancer (NSCLC) to look for genetic driver mutations. The objective of the current study was to evaluate the performance of extended NGS panels using EBUS-TBNA samples in a real-world setting and identify factors associated with the success of NGS. MATERIALS AND METHODS: This study included all patients who underwent EBUS and were diagnosed with non-squamous NSCLC with mediastinal metastasis from 2016 to 2019 at the University of Pennsylvania. We reviewed demographic information, imaging studies, procedure reports, pathology and NGS reports. Logistic regression was used to analyze factors associated with the success of NGS panels. RESULTS: The success rates of NGS using EBUS-TBNA samples were 92.5%, and 91.5% for DNA and RNA NGS panels respectively. Samples from higher N stage (N2 and N3 lymph nodes) and with higher tumor cellularity (>25%) resulted in higher success rate for DNA NGS. The effect of tumor cellularity remained borderline significant after entering multivariable logistic regression. The short-axis diameter of the sampled lymph node on CT scan, FDG-avidity on PET CT and >3 EBUS passes per lymph node during the procedure were not associated with NGS success. CONCLUSION: Both DNA and RNA extended-panel NGS had high performance using EBUS-TBNA samples. Sampling more advanced nodal stations and obtaining samples with higher tumor cellularity were associated with higher success rate of DNA NGS. Other imaging or procedural factors did not affect NGS performance.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 2: a survey of the American Society of Cytopathology community.

INTRODUCTION: High-risk human papillomavirus (HR-HPV) status is critical in the diagnosis of oropharyngeal squamous cell carcinoma, informing prognosis and choice of therapy. HR-HPV status additionally plays a key role in the evaluation of squamous cell carcinoma of unknown origin metastatic to cervical lymph nodes. Thus, HR-HPV testing of fine needle aspirate (FNA) specimens from the head and neck is invaluable for accurate diagnosis, prognostication, and treatment planning. MATERIALS AND METHODS: American Society of Cytopathology members were surveyed to understand the current state of HR-HPV testing on FNA samples from the head and neck. The survey focused on 3 main topic areas: practice setting of respondents, methods of collection and processing of aspirate specimens for HR-HPV testing, and validation of HR-HPV testing methodologies on aspirate samples. RESULTS: The survey reveals that laboratories employ various methods to detect HR-HPV in FNA samples, most commonly p16 immunohistochemical staining of cell block sections. Although some laboratories have independently validated their HR-HPV detection method, such validation is not universal. Finally, not all respondents currently have HR-HPV testing available, but approximately half of those without a testing method desire to make HR-HPV testing of FNA samples available. CONCLUSIONS: Survey responses highlight that various testing modalities are utilized for HR-HPV detection in aspirate samples. However, internal laboratory validation of HR-HPV testing for FNA specimens is not ubiquitous despite professional society recommendations.

Indeterminate Thyroid Fine-Needle Aspirations in Pediatrics: Exploring Clinicopathologic Features and Utility of Molecular Profiling.

INTRODUCTION: The diagnostic utility of molecular profiling for the evaluation of indeterminate pediatric thyroid nodules is unclear. We aimed to assess pediatric cases with indeterminate thyroid fine-needle aspiration (FNA) alongside clinicopathologic features and mutational analysis. METHODS: A retrospective review of 126 patients with indeterminate cytology who underwent FNA between January 2010 and December 2021 at the Children's Hospital of Philadelphia was performed. Indeterminate cases defined by The Bethesda System for Reporting Thyroid Cytopathology (AUS/FLUS or TBSRTC III; FN/SFN or TBSRTC IV; SM or TBSRTC V) were correlated to clinicopathologic and genetic characteristics. RESULTS: Of the 114 surgical cases, 48% were malignant, with the majority of malignant cases diagnosed as follicular variant of papillary thyroid carcinoma (28/55). Risk of malignancy increased with TBSRTC category: 23% for AUS/FLUS, 51% for FN/SFN, and 100% for SM nodules. There were significant differences in surgical approach (p < 0.01), performance of lymph node dissection (p < 0.01), histological diagnosis (p < 0.01), primary tumor focality/laterality (p = 0.04), and lymphatic invasion (p = 0.02) based on TBSRTC classification, with resultant differences in post-surgical risk stratification per American Thyroid Association (ATA) Pediatric Guidelines (p = 0.01). Approximately 89% (49/55) of cases were classified as ATA low risk, and 5 of 6 patients with ATA intermediate- or high-risk disease had SM cytology. Somatic molecular testing was performed in 40% (51/126) of tumors; 77% (27/35) of malignant cases and 38% (6/16) of benign cases harbored driver alteration(s). Of the driver-positive malignant cases, 52% (14/27) were associated with low risk (DICER1, PTEN, RAS, and TSHR mutations), 33% (9/27) were associated with high risk (BRAF mutations and ALK, NTRK, and RET fusions), and 15% (4/27) had unreported risk for invasive disease (APC, BLM, and PPM1D mutations and TG-FGFR1 fusion). Incidence of high-risk drivers increased with TBSRTC category. Approximately 23% (8/35) of patients harboring thyroid malignancy did not have an identifiable driver alteration. CONCLUSIONS: Molecular analysis is useful to discriminate benign and malignant thyroid nodules with indeterminate cytology. Patients with driver genetic alteration(s) and indeterminate cytology should consider surgical management secondary to the high incidence (82%; 27/33) of thyroid malignancy in these patients.

Cross-contamination in cytology processing: a review of current practice.

INTRODUCTION: New cytopreparatory technologies decrease the need for direct smears in favor of an increased use of liquid-based cytology methods. Despite these practice changes, Clinical Laboratory Improvement Amendments continue to require that cytopathology laboratories have procedures to prevent cross-contamination (CC). While the incidence of CC is not well documented, specific cytologic preparations and specimens with a high potential for CC have not been generally defined by professional guidelines or consensus. The American Society of Cytopathology Clinical Practice Committee surveyed cytology practitioners to better understand current practice related to CC in cytology. MATERIALS AND METHODS: The survey focused on four topics: (1) practice settings and demographic data; (2) current practice for meeting CC requirements; (3) practice for rapid on-site evaluation; and (4) preparation types considered high risk for CC. The survey was sent to all American Society of Cytopathology and American Society for Cytotechnology members from July 1 to August 14, 2020. RESULTS: Ninety-eight percent of laboratories had a written CC policy, with 66.18% of the policies addressing rapid on-site evaluation CC procedures. Documented cases of CC were rare. Alcohol-fixed, direct smears of Pap-stained fluids were deemed the most likely to be impacted by CC. Cell block contamination during the histologic processing were reported by 56.20% of respondents. CONCLUSIONS: Changes in practice has resulted in decreased preparation types associated with a high potential for CC. Laboratories should follow a risk-based approach to define these cases. Knowledge of practice patterns among laboratories can guide the development and refinement of policy and procedures.

Utility of Fine-Needle Aspirations to Diagnose Pediatric Thyroid Nodules.

INTRODUCTION: Risk of malignancy for pediatric thyroid nodules classified according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is not well defined. Correlations between risk of malignancy and ancillary clinical data remain inconclusive. We report a single institutional experience of fine-needle aspiration (FNA) to improve upon current management paradigm of thyroid nodules. METHODS: A retrospective chart review of 575 thyroid nodules was performed of 324 patients who underwent 340 FNAs between 2008 and 2018 at the Children's Hospital of Philadelphia. Demographics, ultrasound (US) characteristics, FNA cytology, surgical pathology, and ancillary data were reviewed. RESULTS: The rate of malignancy according to TBSRTC was 0.0% for category I, 0.8% for category II, 15.6% for category III, 54.5% for category IV, 100.0% for category V, and 100.0% for category VI. The cumulative Thyroid Imaging Reporting and Data System (TI-RADS) score was significantly correlated with benign and malignant nodules on pathology (p < 2.2e-16). Distribution of TI-RADS for cytologically indeterminate nodules with benign or malignant pathology revealed significant differences for composition (p = 3.20e-8) and echogenic foci (p = 0.005) but not for echogenicity (p = 0.445), shape (p = 0.160), margins (p = 0.220), and size (p = 0.105). Distributions of thyroid-stimulating hormone levels between benign and malignant patients was significant (p = 1.58e-3). CONCLUSIONS: Nodules with TI-RADS scores >3 should undergo FNA, irrespective of size; surgical resection is recommended for nodules classified as TBSRTC category IV and V due to high risk of malignancy. US surveillance instead of FNA can be performed for nodules with TI-RADS scores ≤3.

Results from the 2019 American Society of Cytopathology survey on rapid onsite evaluation (ROSE)-part 2: subjective views among the cytopathology community.

INTRODUCTION: This study aims to improve understanding of the cytopathology community's perspective regarding the value of rapid onsite evaluation (ROSE) in clinical practice. MATERIALS AND METHODS: The American Society of Cytopathology membership was surveyed in 2019 to obtain subjective data on the cytopathology community's perceptions regarding ROSE. Comments were categorized by major themes and attitudes and analyzed by respondent's role in laboratory, practice size, and practice setting (Fisher's exact and χ2 tests). RESULTS: A total of 541 responses were received from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 trainees, and 6 others (as previously reported). Reasons for which cytopathology personnel provide this service aligned with their perceptions of why clinicians request ROSE. A minority of respondents, disproportionally from high volume centers, felt ROSE is unnecessary. Overall attitude regarding ROSE was generally positive. There were no significant differences in attitude regarding ROSE according to role in laboratory or practice size, but respondents from academic centers provided a significantly higher percentage of positive comments than those in private or community practice. Although survey respondents generally felt that ROSE is valuable to patient care, they also highlighted several challenges, including staffing, time commitment, and inadequate reimbursement. Implementation of telecytology was felt to potentially alleviate some of these challenges. CONCLUSIONS: Survey results show that the cytology community views ROSE favorably, practices vary considerably, and there is a perceived need for improved reimbursement. Data from this study may be used to identify areas that warrant additional research to clarify the clinical value of ROSE.

Results from the 2019 American Society of Cytopathology survey on rapid on-site evaluation-Part 1: objective practice patterns.

INTRODUCTION: Rapid on-site evaluation (ROSE) is a service provided by cytologists that helps ensure specimen adequacy and appropriate triage for ancillary testing. However, data on the current usage patterns across different practice settings have been lacking. MATERIALS AND METHODS: To obtain an accurate and timely assessment of the current state of practice of ROSE, a 14-question online survey was constructed by the Clinical Practice Committee of the American Society for Cytopathology. The survey was available to the membership of the American Society for Cytopathology for a 3-week period in early 2019. RESULTS: A total of 541 responses were received, including from 255 cytopathologists/pathologists, 261 cytotechnologists, 19 cytology resident/fellow trainees, and 6 others. ROSE was offered as a clinical service by 95.4% of the respondents, with telecytology for ROSE used in 21.9% of the practices. Endobronchial ultrasound-guided transbronchial needle aspiration was the procedure most frequently reported to use ROSE (mean, 59.1%; median, 70%). Cytotechnologists were involved in ROSE in most practices. The number of daily ROSE procedures correlated with the annual nongynecologic cytology volumes. Approximately 70% of ROSE procedures were reported to require >30 minutes, on average, for the cytologist. CONCLUSIONS: The results from our survey of cytologists have shown that the reported practice patterns for the usage of ROSE vary considerably. The presented data can help inform future guideline recommendations and the implementation of ROSE in different clinical settings.

Preoperative cytologic interpretation of noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a 1-year multi-institutional experience.

INTRODUCTION: Encapsulated follicular variant of papillary thyroid carcinoma (PTC) has an indolent behavior; hence, a change in terminology to "noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)" has been proposed. Data are scant on the fine-needle aspiration (FNA) diagnosis of nodules proven to be NIFTP upon resection. The aim was to evaluate the FNA diagnosis of nodules diagnosed as NIFTP upon resection. MATERIALS AND METHODS: The archives of 8 participating institutions were searched for thyroid resection specimens obtained in a 1-year period, and pertinent demographic and pathology data were recorded. RESULTS: 2226 thyroid surgeries were performed over the indicated time period. NIFTP was diagnosed in 6.3% of cases; 118 patients (119 nodules) with NIFTP and available preoperative thyroid FNA were included. Preoperative cytologic diagnosis were: non-diagnostic: 0.8%; benign: 5.9%; atypia of undetermined significance/follicular lesion of undetermined significance: 42.9%; follicular neoplasm/suspicious for a follicular neoplasm: 31.0%; suspicious for malignancy: 15.9%; malignant: 3.4%. Molecular data was available for 49 cases, either by Afirma or ThyGenX/ThyroSeq. Of the Afirma cases, 11% were classified as "benign", 2% as "indeterminate", and 87% as "suspicious"; of the ThyGenX/ThyroSeq cases, 50% had NRAS mutations, 20% demonstrated KRAS mutations, 20% showed HRAS mutations, and 10% showed a BRAF mutation (K601E). CONCLUSIONS: NIFTP are tumors demonstrating nuclear features similar to those seen in PTC. Our series shows that a preoperative diagnosis of "suspicious for malignancy" or "malignant" is uncommon in NIFTP, suggesting that there are sufficient cytomorphologic differences between PTC and NIFTP to allow for the suspicion of NIFTP on FNA specimens.

The utility of adaptive eLearning in cervical cytopathology education.

BACKGROUND: Adaptive eLearning allows students to experience a self-paced, individualized curriculum based on prior knowledge and learning ability. METHODS: The authors investigated the effectiveness of adaptive online modules in teaching cervical cytopathology. eLearning modules were created that covered basic concepts in cervical cytopathology, including artifacts and infections, squamous lesions (SL), and glandular lesions (GL). The modules used student responses to individualize the educational curriculum and provide real-time feedback. Pathology trainees and faculty from the authors' institution were randomized into 2 groups (SL or GL), and identical pre-tests and post-tests were used to compare the efficacy of eLearning modules versus traditional study methods (textbooks and slide sets). User experience was assessed with a Likert scale and free-text responses. RESULTS: Sixteen of 17 participants completed the SL module, and 19 of 19 completed the GL module. Participants in both groups had improved post-test scores for content in the adaptive eLearning module. Users indicated that the module was effective in presenting content and concepts (Likert scale [from 1 to 5], 4.3 of 5.0), was an efficient and convenient way to review the material (Likert scale, 4.4 of 5.0), and was more engaging than lectures and texts (Likert scale, 4.6 of 5.0). Users favored the immediate feedback and interactivity of the module. Limitations included the inability to review prior content and slow upload time for images. Learners demonstrated improvement in their knowledge after the use of adaptive eLearning modules compared with traditional methods. CONCLUSIONS: Overall, the modules were viewed positively by participants. Adaptive eLearning modules can provide an engaging and effective adjunct to traditional teaching methods in cervical cytopathology. Cancer Cytopathol 2018;126:129-35. © 2017 American Cancer Society.

Fine-needle aspiration cytology of endometriosis.

Endometriosis commonly involves the pelvis, but may also present as a palpable mass in extrapelvic sites, such as the abdominal wall or inguinal region, where it can be evaluated by fine needle aspiration (FNA). In this report, we illustrate the findings seen in seven cases of endometriosis diagnosed by FNA in patients with a chief complaint of pain associated with an abdominal wall or pelvic mass, occurring in a setting of prior pelvic surgery. The most common previous surgery was Cesarean section (n = 6), followed by hysterectomy (n = 2), and hernia repair (n = 1). In all cases, cytologic examination revealed a glandular component composed largely of orderly fragments of cohesive epithelial cells, a spindle cell stromal component presenting either as loosely organized tissue fragments or single cells, and rare hemosiderin-laden macrophages. Four cases showed focal cytologic atypia in the glandular component with extreme nuclear atypia identified in two of these cases. Atypical features included nuclear crowding and disorganization, nuclear enlargement, hyperchromasia with irregular chromatin distribution and anisonucleosis, raising the possibility of a coexistent malignancy and recommendation for excision. Although malignancy was not identified in follow-up surgical excision specimens, the wide range of cytomorphologic changes that can be seen in FNA specimens of endometriosis should be recognized. Diagn. Cytopathol. 2017;45:359-363. © 2016 Wiley Periodicals, Inc.

Using "residual" FNA rinse and body fluid specimens for next-generation sequencing: An institutional experience.

BACKGROUND: Tissue specimens are typically considered optimal for molecular testing; however, in the current era of personalized medicine, cytopathology specimens are increasingly recognized as potential sources for molecular testing. This is often accomplished by using cell block specimens and/or fine-needle aspiration (FNA) smear preparations. In this study, the authors investigated the feasibility, performance, and quality of "residual" FNA rinse and body effusion fluids used for next-generation sequencing (NGS). METHODS: Sequence data were generated from 17 malignancies in 16 patients from 13 FNA (10 lymph nodes, 1 lung, and 2 bone lesions) and 4 effusion (3 pleural and 1 pericardial) specimens. Malignancies included carcinomas (lung, breast, ovarian, and unknown primary), melanoma, and myeloma. Paired NGS testing was performed in 7 patients who had surgical biopsy or cell block specimens available. Routinely processed residual FNA rinse material and body fluids were used for DNA extraction and NGS (targeted gene panel). RESULTS: NGS was successfully performed on all 17 specimens. A significant amount of DNA was obtained from the residual FNA rinse (176.3 ng/µL) compared with the paired cell block slides (10.6 ng/µL). Two of the 10 lung adenocarcinomas (20%) demonstrated epidermal growth factor receptor (EGFR) mutations, including 1 leucine-to-arginine substitution at codon 858 (L858R) in exon 21 and 1 codon 2235_2249 deletion (resulting in an in-frame deletion of 5 amino acids from position 746 to 750 [glutamic acid, leucine, arginine, glutamic acid, and alanine]; E746_A750del) in exon 19. Three KRAS [Kirsten rat sarcoma viral oncogene homolog] mutations, 1 BRAF (v-Raf murine sarcoma viral oncogene homolog B1) mutation, and 1 NRAS (neuroblastoma RAS viral oncogene homolog) mutation were identified in the remaining lung adenocarcinomas. Patients who underwent paired testing demonstrated 100% concordant mutations. CONCLUSIONS: Targeted NGS can be performed on residual FNA rinse and body fluid specimens. This approach is particularly important when a paucicellular cell block or biopsy specimen is encountered. Cancer Cytopathol 2016;124:324-29. © 2015 American Cancer Society.

Thyroid nodule fine-needle aspiration.

Thyroid nodules are a common clinical problem and are noted much more commonly on imaging examinations than are apparent by palpation. Fine-needle aspiration biopsy (FNA), which yields a cytology specimen for analysis, is the standard test to determine whether surgical removal of a detected nodule is recommended. This article will review the current guidelines for recommending FNA of thyroid nodules, the technique and risk of the procedure, and the implications for patient care based on FNA results. FNA has an essential role in the evaluation of patients with thyroid nodules to reduce the rate of unnecessary thyroid surgery for patients with benign nodules and triage patients with thyroid cancer to appropriate surgery. Before the routine use of FNA, approximately 14% of resected thyroid nodules were malignant, whereas with the current widespread use of thyroid nodule FNA, >50% of resected thyroid nodules are malignant. Historically, thyroid nodules were identified by physical examination of the neck, with a prevalence of approximately 5%-10% of adults in the United States, and these patients underwent palpation-guided FNA in the physician's office. In recent years, the increased use of sonography to examine the thyroid as well as cross-sectional imaging of the neck by computed tomography and magnetic resonance imaging has resulted in the detection of many nonpalpable nodules. In older adults, thyroid nodules may be detected in >67% of people screened by sonography. Fortunately, the vast majority of nodules are benign, but when they are discovered, an assessment regarding the need to exclude malignancy using FNA must be performed.

Low-dose cyclophosphamide associated with hemorrhagic cystitis in a breast cancer patient.

Hemorrhagic cystitis is a known complication of high-dose cyclophosphamide treatment, generally occurring at doses greater than 100 g. There are few reports of hemorrhagic cystitis occurring with low-dose cyclophosphamide therapy, and this complication has not been described in breast cancer patients. We present a case of a patient with stage IIB breast cancer who developed clinical, radiographic, and pathologic evidence of hemorrhagic cystitis after a single 600 mg/m(2) dose of cyclophosphamide. Three subsequent cycles of cyclophosphamide with the addition of IV hydration and MESNA were given without complication, and the patient's urologic symptoms resolved. Repeat cystoscopy demonstrated pathologic resolution of the cystitis. We review the literature regarding proposed mechanisms of hemorrhagic cystitis, and discuss the applicability of these hypotheses in our patient.

Subtype distribution of human papillomavirus in HIV-infected women with cervical intraepithelial neoplasia stages 2 and 3 in Botswana.

Human papillomavirus (HPV) vaccines containing types 16 and 18 are likely to be effective in preventing cervical cancer associated with these HPV types. No information currently exists in Botswana concerning the HPV types causing precancerous or cancerous lesions. Our goal was to determine the prevalence of HPV types associated with precancerous cervical intraepithelial neoplasia (CIN) stages 2 and 3 in HIV-infected women in Gaborone, Botswana. HIV-infected women referred to our clinic with high-grade intraepithelial lesion on the Pap smear were enrolled in the study. HPV typing was only performed if the histopathology results showed CIN stage 2 or 3 disease using linear array genotyping (CE-IVD, Roche Diagnostics). One hundred HIV-infected women were identified with CIN stages 2 or 3 between August 11, 2009 and September 29, 2010. Eighty-two of 100 women enrolled had coinfection by multiple HPV subtypes (range, 2 to 12). Of the remaining 18 women, 14 were infected with a single high-risk subtype and 4 had no HPV detected. Overall, 92 (92%) women were infected with at least 1 high-risk HPV subtype, and 56 were coinfected with more than 1 high-risk HPV type (range, 2 to 5). Fifty-one (51%) women had HPV subtypes 16, 18, or both. HPV 16 and 18 are the most common types in HIV-infected women with CIN 2 or 3 in Gaborone, Botswana, suggesting that the implementation of HPV vaccination programs could have a significant impact on the reduction of cervical cancer incidence. However, given the relative lack of knowledge on the natural history of cervical cancer in HIV-infected women and the significant prevalence of infection and coinfection with other high-risk HPV types in our sample, the true impact and cost-effectiveness of such vaccination programs need to be evaluated.

Vaginal intraepithelial neoplasia (VAIN) after radiation therapy for gynecologic malignancies: a clinically recalcitrant entity.

OBJECTIVES: Vaginal dysplasia is associated with prior radiation therapy (RT) for gynecologic malignancies. We reviewed our institution's experience with VAIN in patients who were treated with radiation therapy for a gynecologic malignancy. METHODS: A retrospective review of patients treated for VAIN was performed. All cases of patients followed and treated for VAIN after radiation therapy were identified (n=10), along with a cohort of patients with VAIN who did not have radiation therapy (n=23). RESULTS: Mean follow-up after initial diagnosis of VAIN was 37.6 months (range: 12 to 72). Cytologic screening events after diagnosis of VAIN (n=105) showed that patients with prior RT were more than twice as likely to have recurrent dysplasia (OR 3.625, 95% CI=from 1.454 to 9.0376) after treatment. Of patients who recurred, the mean time to first recurrence was 12.3 months in cases and 15.3 months in controls, which was not statistically significant (p=0.31). Screening practices at our institution ranged from 3 month to 12 month intervals. 3 patients in the RT group and 1 patient in the control group developed invasive squamous cell cancer of the vagina. CONCLUSIONS: Vaginal dysplasia after radiation therapy is more refractory to treatment than dysplasia not associated with radiation therapy, more likely to recur after surgical and ablative therapy, and may also be more likely to progress to invasive cancer. These data support the need for further study to determine the optimal follow-up screening interval and whether aggressive surgical or ablative treatment stems disease progression in this clinical scenario.

Value of P63 and CK5/6 in distinguishing squamous cell carcinoma from adenocarcinoma in lung fine-needle aspiration specimens.

The current FDA-approved standard of care for nonsmall cell lung cancer is Carboplastin/Taxol/Avastin based upon an impressive survival benefit; however, patients with squamous carcinoma (SQCC) cannot receive Avastin because of a 30% mortality rate due to fatal hemoptysis. In this study we evaluated the role of cytomorphology and immunohistochemistry in differentiating SQCC from adenocarcinoma (ADC) in lung FNA specimens. The case cohort included 53 FNA cases of nonsmall cell lung carcinoma with surgical pathology follow-up. All FNA specimens were reviewed independently by a panel of cytopathologists to differentiate between SQCC and ADC. The cell block material was available in 23 cases (11 ADC and 12 SQCC) to perform immunohistochemical stains for TTF-1, CK7, CK20, P63, and CK5/6. On surgical resection, 35/53 (66%) cases were diagnosed as ADC and 18/53 (34%) as SQCC. The number of cases classified correctly on the basis of cytomorphology was 66% for ADC and 53% for SQCC (combined accuracy 60%). By immunohistochemical staining, 14/23 (61%) cases expressed TTF-1. Nine cases were TTF-1 negative; eight of the TTF-1 negative cases (89%) were SQCC. Twenty-three cases expressed CK7 (87%); one ADC case (4%) showed focal CK20 positivity. Both P63 and CK5/6 expression was seen in 9/12 (75%) SQCC cases; none of the ADC cases showed this dual expression. Cytomorphology alone may not be able to stratify all cases of nonsmall cell lung carcinoma into ADC and SQCC in FNA specimens. The immune-panel of TTF-1, CK7, CK20, P63, and CK5/6 is useful in differentiating SQCC from ADC.

Acute promyelocytic leukemic involvement of the optic nerves following mitoxantrone treatment for multiple sclerosis.

Mitoxantrone, the first immunosuppressant to receive FDA approval for treatment of worsening relapsing-remitting, secondary progressive, and progressive-relapsing multiple sclerosis (MS) is a DNA topoisomerase II inhibitor that has been associated with the development of acute promyelocytic myelogenous leukemia (APML). Central nervous system APML is a rare site of extramedullary involvement following mitoxantrone therapy. We report a patient with history of multiple sclerosis who developed bilateral optic nerve involvement as the primary manifestation of APML relapse following mitoxantrone treatment.