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Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is increasing in incidence and is often first diagnosed on a cytology fine needle aspiration (FNA) specimen of metastatic nodal disease of the neck. In the setting of oropharyngeal squamous cell carcinoma, HPV status defines the disease with HPV-associated tumors having better overall prognosis than those that are HPV negative. Furthermore, metastatic squamous cell carcinoma of the neck of unknown origin requires testing for HPV as a positive result suggests an oropharyngeal primary. As a result, HPV testing in aspirate samples is increasingly important for the proper diagnosis and treatment of patients with head and neck squamous cell carcinoma. Although HPV testing in cervicovaginal cytology specimens is common and well-established, testing in head and neck FNA samples remains challenging. p16 immunohistochemistry is an excellent surrogate marker for HPV in tumors of known or suspected oropharyngeal origin, but the criteria used in histologic specimens may not be appropriate in cytology samples. FNA samples are more frequently hypocellular, and cytology cell blocks have variable fixation and processing steps, limiting the utility of p16 immunohistochemistry. Other potential testing options have been reported in the literature including staining of aspirate smears and molecular testing of liquid-based samples. The American Society of Cytopathology Clinical Practice Committee recently surveyed the American Society of Cytopathology membership to determine the current state of HPV testing in aspirate samples, and this review article is designed to provide a summary of the current literature on various testing options in FNA samples.

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.

The International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy (FNAB) Cytology reporting system is an initiative of the IAC that seeks to provide a comprehensive, standardized approach to breast FNAB reporting to facilitate reproducible cytopathology reporting and to establish best practice guidelines. The system is evidence-based, supports a structured reporting format and will aid in maximizing the usefulness of the FNAB technique and optimizing communication with the clinical team and the patient.

The liquid-based cytology (LBC) technique is an automated method for preparing thin-layer cytological samples from cell suspensions collected in alcohol-based preservative. LBC preparations of breast fine needle aspiration biopsies (FNAB) demonstrate better cellular preservation, less cell overlapping, and elimination of excessive blood and inflammation compared with conventional smears (CS). Conversely, alterations in architecture and cell morphology as well as loss of myoepithelial cells and stromal elements have been described in LBC preparations. Similar accuracy for LBC and CS has been demonstrated in different studies. However, LBC requires specific training before applying this technique. LBC is suitable for ancillary testing. This chapter presents the general cytomorphological features of breast FNAB in LBC and then the findings in specific lesions.

Giardiasis is the most common intestinal parasitic infection in the United States. The organism elicits no, or minimal, inflammatory changes in duodenal biopsy samples, so it can be easily overlooked. We performed this study to determine whether Giardia could be isolated from the formalin fixative of biopsy samples, and to evaluate the value of fluid analysis in the assessment for potential infection. We prospectively evaluated duodenal biopsy samples from 92 patients with a clinical suspicion of giardiasis or symptoms compatible with that diagnosis (ie, diarrhea, bloating, or abdominal pain) Biopsy samples were routinely processed and stained with hematoxylin and eosin. Histologic diagnoses included giardiasis (5 cases, 4%), normal findings (64 cases, 70%), peptic injury/active duodenitis (12 cases, 13%), and intraepithelial lymphocytosis with villous blunting (10 cases, 12%). Fifteen cases (13%) showed detached degenerated epithelial cells or mucus droplets in the intervillous space that resembled Giardia. Cytology slides were prepared from formalin in the biopsy container using the standard Cytospin protocol and reviewed by a cytopathologist blinded to the biopsy findings. Cytologic evaluation revealed Giardia spp. in all 5 biopsy-proven cases, and identified an additional case that was not detected by biopsy analysis. Organisms were significantly more numerous (mean: 400 trophozoites; range, 120 to 810) and showed better morphologic features in cytology preparations compared with tissue sections (mean: 129 trophozoites; range, 37 to 253 organisms; P=0.05). Our findings suggest that cytology preparations from formalin fixative can resolve diagnostically challenging cases and even enhance Giardia detection in some cases.

Background Minimally invasive diagnostic procedures such as needle-core biopsy and fine-needle aspiration provide adequate material for molecular analyses. Advances in precision oncology are trending toward the interrogation of limited amounts of genomic material to guide clinical and therapeutic decisions. The aim of this study was to investigate the minimum cellularity needed on cytologic smears for the identification of clinically relevant variants with next-generation sequencing (NGS). Methods Thirty cases of cytologically diagnosed, resection-proven primary lung adenocarcinoma were identified. Nineteen of the 30 cases were known to harbor actionable variants. One Diff-Quik (DQ)-stained slide and 1 Papanicolaou (Pap)-stained slide were selected from each case. Cases were categorized as containing fewer than 100 tumor cells, 100 to 500 tumor cells, or more than 500 tumor cells. NGS was performed on the Ion Torrent platform. Results NGS was successfully performed on all cell blocks and on 90% of the smears. Paired DQ and Pap smears showed similar cellularity, and cases that differed in cellularity were within 1 category of each other. The cases with more than 100 tumor cells had a 93% success rate; this was significantly different from the situation for cases with fewer than 100 tumor cells, which were successfully sequenced only 67% of the time. Overall, NGS was able to provide clinically relevant information for 83% of DQ smears and for 90% of Pap smears tested. Conclusions The data show a significantly higher likelihood of successful NGS with cytologic smears with more than 100 tumor cells. There was a trend for a higher NGS success rate with Pap smears versus DQ smears. Cancer Cytopathol 2017;125:398-406. © 2017 American Cancer Society.

The majority of thyroid nodules are benign, but a small percentage, about 10–15%, are malignant. According to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), 3% of all thyroid fine needle aspiration (FNA) specimens are classified as Suspicious for Malignancy (SM).

Immunocytohistochemistry/immunohistochemistry (ICC/IHC) has become an indispensable tool in the practice of surgical pathology and cytology. In our daily clinical practice, most specimens from thyroid fine needle aspiration (FNA) and liquid-based preparations (LBP) are diagnosed without the routine use of immunostain, but IHC can be used judiciously on the corresponding cell block in certain situations to confirm or rule out a diagnosis. Scraping of thick Diff-Quik (DQ)–stained smears into the CytoLyt/CytoRich Red (collection media for ThinPrep [TP] and SurePath [SP] respectively) at the time of rapid on-site evaluation (ROSE) to prepare the cell block can further enhance the yield, and multiple immunostains can be performed on the cell block if needed.

Thyroid FNA has reduced the rate of unnecessary surgeries for benign thyroid nodules. High negative predictive value (NPV) of a benign FNA diagnosis has made it a valuable initial test for thyroid nodules.

Approximately 5% (2–16%) of all thyroid fine needle aspiration (FNA) results are malignant. PTC is the most common form of thyroid cancer, comprising 83% of all diagnosed thyroid cancers. Diagnostic accuracy of cytology for PTC is high; when a diagnosis of PTC is rendered, 94–96% prove to be PTC on resection.

Thyroid fine needle aspiration (FNA) is well established as a first-line diagnostic procedure in patients with thyroid nodules, but despite improved FNA techniques and increase use of ultrasound (US) guidance, about 20% of initial FNA specimens may be nondiagnostic or unsatisfactory (ND/Unsat). Nondiagnostic FNA of thyroid nodules presents a clinical dilemma, as the nature of the nodule is not clear and the nodule must be re-aspirated for a diagnosis.

Thyroid FNA is a highly accurate modality for initial assessment of a nodule. A benign result has a negative predictive value (NPV) greater than 95%, and a malignant diagnosis has a positive predictive value (PPV) of 94–96%. But in 15% to 30% of cases, FNA renders an indeterminate diagnosis, leading to a clinical management dilemma.

Estimated annual incidence of thyroid nodules in the United States is 0.1%, which translates to 300,000 new nodules every year. Up to 50% of the general population may have sonographically detectable thyroid nodules, although only up to 5% of these harbor a malignancy. The high incidence of thyroid nodules and low rate of cancer among nodules pose a clinical dilemma.

Hurthle cells are follicular-derived oncocytic cells originally described by Askanazy in 1898. They are also referred to as oncocytic, oxyphilic, and Askanazy cells.

Indeterminate diagnoses on FNA is the major limitation of thyroid cytology. The problem results from cytological features overlapping between non-neoplastic and neoplastic follicular lesions, which are reflected by the low concordance among pathologists in the indeterminate category. (See Chaps. 5, 6, and 7).

Parathyroid glands are light yellow to brown and are small (about 2–7 mm). They tend to become prominent in pathological states, most commonly hyperparathyroidism. More than 80% of individuals have four parathyroid glands. Parathyroid glands can be located within other organs, most commonly the thyroid gland, where they are found in the perithyroidal fat.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), a uniform and standardized reporting system for thyroid fine needle aspiration (FNA), was originally established in 2009 and updated in 2017. The system is widely accepted in the United States and globally. It is specifically designed for the reporting of thyroid follicular and C-cell–derived lesions based on clearly outlined diagnostic criteria.

This chapter discusses three other malignant tumors affecting the thyroid: Anaplastic thyroid carcinomas (ATC) Poorly differentiated thyroid carcinoma (PDCa) Primary thyroid lymphoma

Medullary thyroid carcinoma (MTC) represents 1–2% of thyroid carcinomas. MTC occurs in sporadic and familial forms; sporadic MTC accounts for 75% of cases.

Background The tall cell variant of papillary thyroid carcinoma (PTC-TC) has been associated with aggressive features including extrathyroidal extension, higher rate of lymph node and distant metastases, and higher recurrence rate. We aimed to evaluate the cytomorphologic features of PTC-TC on ThinPrep (TP) along with its diagnostic efficacy to detect PTC-TC. Methods Preoperative cytology samples from 30 cases of histologically-proven PTC-TC and 30 classical PTC controls were selected for this study. TP preparations were evaluated for varying architectural and cytomorphologic features. Results Tall cells were present in the majority of PTC-TC cases and were located at the periphery of cell clusters and as single cells. Cytoplasmic cuff along the periphery of cell clusters and soap-bubble pseudoinclusions were very specific features of PTC-TC, when present. PTC-TC cases were more likely to show abundant oncocytic cytoplasm and distinct cell borders. Cytoplasmic tails were more likely to be present and more numerous in PTC-TC. The presence of nuclear grooves, papillary architecture, and giant cells were not reliable distinguishing features of PTC-TC vs controls. Conclusion Our results indicate that tall cell cytomorphologic and architectural features in PTC are identifiable on TP.

BACKGROUND Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited. METHODS Relevant records of all pericardial effusions from January 2008 to September 2014 were examined and compared with pericardial biopsy results when performed. Discrepant cases were reviewed to determine the cause of the disagreement. RESULTS In total, 419 pericardial effusion specimens obtained from 364 patients were examined. Cytologic diagnostic categories included: negative for malignancy (332 specimens; 79%), equivocal (25 specimens; 6%), and positive (62 specimens from 51 patients; 15%). Forty-seven patients who had positive effusions were known to have malignancy. The most common primary malignancies were breast (39.3%) and lung (39.3%) cancers in women and lung cancer (47.4%) in men. A concurrent pericardial biopsy was performed in 46% of patients. Excluding equivocal cytologic diagnoses, cytology and biopsy were concordant in 153 of 173 paired samples (88.4%). The sensitivity of cytology in diagnosing malignancy was 92.1% compared with 55.3% for pericardial biopsy. CONCLUSIONS Cytologic examination has significant diagnostic utility in the evaluation of pericardial effusions and exhibits a lower false-negative rate compared with pericardial biopsy. Submission of pericardial biopsy alongside effusion cytology is associated with increased sensitivity for detecting malignancy and may be especially useful in the setting of low-volume pericardial effusion. Cancer Cytopathol 2016. © 2016 American Cancer Society.

The Papanicolaou Society of Cytopathology has developed a set of guidelines for pulmonary cytology including indications for bronchial brushings, washings and endobronchial ultrasound-guided fine needle aspiration, technical recommendations for cytologic sampling, recommended terminology and classification scheme, recommendations for ancillary testing and recommendations for postcytologic diagnosis management and follow-up. All recommendation documents are based on the expertise of the authors, extensive literature review and feedback from presentations at national and international conferences. This document selectively presents the results of these discussions. The present document summarizes the recommendations for clinical and imaging evaluation of pulmonary lesions along with the indications for cytologic studies regarding these abnormalities. Preprocedural requirements regarding brushing, washing and needle aspiration procedures are discussed also. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

Introduction Urothelial carcinoma (UCC) of the bladder is the most common malignancy of the urinary tract. The performance of urine cytology (UCy) after radical cystectomy (RC) and urinary diversion is quite variable and there is no consensus regarding its role in post-treatment surveillance. The goal of this study is to retrospectively review the diagnostic value of positive (suspicious or positive for malignancy) diverted urine cytology (DUCy) in the detection of urinary tract recurrence of UCC. Materials and Methods A retrospective 10-year (January 2005 to January 2015) computerized search for all DUCy specimens was conducted. All suspicious (Susp) or positive for malignant cells (PMC) ThinPrep cases were identified and retrospectively reviewed. Clinical, surgical, and pathological follow-up for patients with Susp or PMC UCy were tabulated and analyzed. Results During the 10-year-period, 1,525 DUCy cases from 408 patients were identified. Of these, 25 cases (1.64%) from 10 patients were called either Susp (13; 0.85%) or PMC (12; 0.79%). The 25 DUCy cases occurred within a mean of 20 months post-RC. Out of 10 patients, 9 had a concurrent biopsy or a subsequent resection of the recurrent site. Of these 9 patients, 8 (89%) had subsequent biopsy or resection, which showed recurrent UCC. In 5/8 patients, positive DUCy was the very first manifestation of recurrence, which was subsequently confirmed by imaging or histology. Conclusion It is our experience that patients with positive UCy after RC have a high likelihood of recurrent UCC and should be counseled and managed accordingly. Diagn. Cytopathol, 2016. © 2016 Wiley Periodicals, Inc.

Introduction Ultrasonography-guided fine-needle aspiration (US-FNA) yields diagnostic material more often than palpation-guided FNA does. It is often performed by an interventional radiologist (IR) but rarely by a cytopathologist (CP). Herein we describe our method of performance and growing experience with this technique. Materials and methods Data from US-FNA of head and neck lesions performed over a 33-month period by both a CP and an IR were reviewed. Special attention was paid to cases for which histologic follow-up was available. Association in concordance between cytologic and histologic diagnoses was attempted using Fisher's exact test. Mean size of masses biopsied, number of passes performed, and passes needed to achieve adequacy were compared between groups using the Wilcoxon rank-sum test. Tests were 2-sided with P Results Of the 175 US-FNAs performed, 108 (62%) were done by the CP and 67 (38%) by the IR. Fifty-eight patients had histologic follow-up; 37 (64%) for the CP and 21 (36%) for the IR. Mean mass size was significantly smaller for the IR at 2.11 cm versus 2.9 cm for the CP ( P = 0.021). Adequacy was achieved after 1 pass in 70% of cases (26 of 37) by the CP and 67% (14 of 21) by the IR. Number of passes performed did not vary significantly between groups. A variety of masses were biopsied; however, the small sample size precluded meaningful evaluation of cytologic concordance to final histology. Conclusions CP-performed US-FNA has been successfully delivered to clinicians at our institution.

Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma-related deaths in women worldwide [1]. Fine needle aspiration (FNA) continues to play an integral part in the pre-operative assessment of a breast mass [2, 3] and is the least invasive, fastest, and most cost-effective technique available. Although needle core biopsy (NCB) has largely replaced FNA for diagnosing most solid breast lesions, particularly in the USA, FNA is still used in most countries and displays good clinical performance [1–4].

Objective: To evaluate the Weill Cornell Medical College (WCMC)/New York Presbyterian Hospital (NYPH) experience with intraoperative frozen (IOF) section in the management of thyroid nodules with a fine needle aspiration (FNA) diagnosis of Bethesda IIâVI and to analyze the cost and pathology benefit it provides. Methods: The surgical and cytopathology files at WCMC/NYPH were searched within the time period of January 2008 to May 2013. A total of 435 thyroid specimens were identified for which both an FNA and subsequent IOF section was performed. The FNA was correlated with the locations of the resected nodule and the nodule frozen for intraoperative diagnosis. The results of the FNA were compared to the IOF section diagnosis and final diagnosis (FD). Results: Among 435 cases, the FNA diagnosis was Bethesda II: 149 cases, Bethesda III: 170 cases, Bethesda IV: 91 cases, Bethesda V: 19 cases, and Bethesda VI: 6 cases. There were a total of 83 carcinomas identified on FD, which included 69 papillary thyroid carcinomas (PTCs), 12 follicular carcinomas, and 2 poorly differentiated carcinomas. The preoperative FNA diagnosis for these carcinomas was as follows: Bethesda II, 11/149 (7.4%), Bethesda III, 24/170 (14%), Bethesda IV, 26/91 (29%), Bethesda V, 16/19 (84%), and Bethesda VI, 6/6Â (100%). IOF section contributed to the diagnosis of malignancy in 16/429 (4%) cases: 1/149 (0.7%) Bethesda II, 5/170 (3%) Bethesda III, 2/91 (1.1%) Bethesda IV, and 8/19 (42%) Bethesda V. The diagnosis of malignancy was confirmed in the 6 Bethesda VI cases by IOF section. There were no false positives on IOF section. IOF had a sensitivity and specificity of 26% and 100%, respectively. Conclusion: The role of IOF section is limited in the evaluation of thyroid nodules. IOF section is most useful for nodules with an FNA diagnosis of Bethesda V lesions. The diagnosis of follicular variant of PTC remains difficult on frozen section. Keywords: Thyroid, Nodule, Frozen section, Fine-needle aspiration, Sensitivity, Specificity

Women ≥30 years of age with negative (-) Pap tests and positive (+) HPV co-test results have a higher prevalence and cumulative risk of developing high-grade cervical intraepithelial neoplasia (CIN 2+). Thus, the current management in these women is to repeat co-test in 12 months or immediate reflex genotyping for HPV16 or HPV 16/18. If genotyping is not an option, timely quality assurance (QA) rescreen of such Pap tests may be a valuable alternative. All ThinPrep Pap tests (TPPT) interpreted as negative for intra epithelial lesion (NILM) or NILM with reactive cellular changes (NILM/RCC) and a (+) high-risk HPV [Hybrid Capture 2 (HC2), Qiagen, Hilden, Germany] co-test result over a 45-month period (10/2009-06/2013) underwent monthly QA review. The TPPT were screened by the TP Imaging System [TIS, Hologic Inc., Bedford, MA]. Twenty five thousand six hundred and seventy five (18%) NILM and NILM/RCC TPPT of a total of 141,548 TPPT underwent HPV co-test. HPV test was (+) in 2,300 (8.9%) TPPT cases. HPV (+) cases by age group were

High grade endometrial stromal sarcoma (HGESS) is an uncommon malignancy recently re-defined in the new WHO classification of endometrial stromal tumors. In this article, we discuss the differential diagnoses of metastatic HGESS in a fine needle aspiration (FNA) of a lymph node and compare the cytomorphology of HGESS in ThinPrep [(TP), Hologic Inc., Boxborough, MA] to conventional smears (CS). The patient had a history of stage I HGESS, status-post supracervical hysterectomy without regional lymph node metastases. Her post-operative course was complicated by pelvic fluid collections and enlarging para-aortic lymph nodes. Diff-Quik (DQ)-stained and Papanicolaou (Pap)-stained smears from a para-aortic lymph node FNA demonstrated a cellular specimen with monomorphic population of plump to oval cells with scant, wispy cytoplasm in aggregates and as single cells. The nuclei showed fine chromatin and small inconspicuous nucleoli. Compared to the CS, HGESS cells in the TP showed similar cytological features, with the exception that the nuclei were slightly smaller, hyperchromatic, and the chromatin pattern was attenuated. In the absence of prior clinical history, the cytomorphology of metastatic HGESS in a lymph node can be difficult to differentiate from a lymphoma, a variety of metastatic spindle cell tumors or metastatic carcinoma. Immunohistochemical analysis and comparison with the primary tumor can be useful in proving the nature of the malignant cells. The cytomorphology of HGESS on TP correlated well in both single cells and aggregates when compared to CS. The differences noted were decreased nuclear size, nuclear hyperchromasia, and slightly attenuated nuclear detail on TP. Diagn. Cytopathol. 2015;43:756–762. © 2015 Wiley Periodicals, Inc.

Riedel thyroiditis is a rare fibrosing disorder characterized by extension of the fibroinflammatory process beyond the thyroid capsule. Due to the nature of this lesion, fine-needle aspiration often yields scant material and may be interpreted as non-diagnostic. In this report, we describe cytologic features that allow the cytopathologist to favor a diagnosis of Riedel thyroiditis, thereby guiding appropriate further work-up and management.

Intercellular bridges may aide in definitive identification of malignant cell origin, especially in squamous cell carcinoma. They are difficult to identify in routine cytologic specimens and are especially rare in smear preparations. Herein, we present images of intercellular bridges from a case of well differentiated squamous cell carcinoma of the esophagus in a cytologic specimen obtained from FNA of a paraesophageal lymph node.

Background There are currently no reliable markers associated with aggressive behavior in well-differentiated and moderately differentiated pancreatic neuroendocrine tumors. We aimed to determine whether expression of ubiquitin carboxyl-terminal hydrolase L1 in conjunction with Ki67 can identify metastatic potential of well-differentiated and moderately differentiated pancreatic neuroendocrine tumors from fine-needle aspiration samples obtained by endoscopic ultrasound. Methods Retrospective review of 48 patients with well-differentiated and moderately differentiated pancreatic neuroendocrine tumors diagnosed by endoscopic ultrasound fine-needle aspiration at a single center identified 35 biopsy samples with adequate material for analysis. Ubiquitin carboxyl-terminal esterase L1 immunocytochemistry of primary pancreatic neuroendocrine tumors was performed along with Ki67 staining and scored semiquantitatively. The combination of ubiquitin carboxyl-terminal esterase L1 score ≤4 (weak) and Ki67 ≥3% (high) was considered a positive test for predicting tumors associated with metastases. Results Weak ubiquitin carboxyl-terminal hydrolase L1 staining had 80% sensitivity, 65% specificity, 63% positive predictive value, and 81% negative predictive value to identify primary tumors associated with metastatic disease. The combination of weak ubiquitin carboxyl-terminal hydrolase L1 staining and high Ki67 staining increased the test specificity to 95%. On multivariable analysis, combined positive test of weak ubiquitin carboxyl-terminal esterase L1 staining and high Ki67 staining was an independent predictor of metastatic disease (P = .047). Conclusion Ubiquitin carboxyl-terminal hydrolase L1 is a novel biomarker for identifying malignant potential of primary well-differentiated and moderately differentiated pancreatic neuroendocrine tumors and in combination with Ki67 is an independent predictor of development of metastatic disease.

The incidence of metastatic carcinoma to the meninges ("meningeal carcinomatosis" [MC]) is increasing due to longer survival of patients and improved imaging techniques. Currently, MC is best diagnosed by cytopathological evaluation of cerebrospinal fluid (CSF). Breast primaries are the commonest cause of MC; although cytopathological features thereof have not been, as yet, fully characterized. In this study of meningeal mammary carcinomatosis, relevant clinicopathological data and archived cytopathological preparations of all "suspicious" and "positive" CSF specimens (1992-2015), from patients with a history of breast carcinoma, were retrieved and reviewed. Twenty-three "positive" CSF specimens, derived from 15 patients formed the basis of this study. All specimens were processed as Cytospin preparations, and stained by Papanicolaou and Diff-Quik techniques. All patients were female, with a mean age of 57 (range: 32-85) years. Mean interval between initial diagnosis of breast carcinoma and "positive" CSF was 32 (range 6-84) months. All 23 specimens (100%) were "cellular" (>10 carcinoma cells). Eighteen (78%) specimens showed only isolated nonclustered cells, and 5 (22%) specimens showed both cell clusters and isolated cells. In most "positive" cases, metastatic breast carcinoma cells showed variation in cell size, with hyperchromatic nuclei, irregular nuclear membranes, prominent nucleoli and cytoplasmic vacuolization. The background in some CSF samples showed red blood cells and fibrin admixed with rare lymphocytes and histiocytes. One specimen showed necrotic debris. Papanicolaou and Diff-Quik-stained Cytospin preparations were equally diagnostic, as the aforementioned findings were present in both types of preparation.

The respiratory tract is comprised of upper and lower airways. The upper airway extends from the sinonasal tract to the larynx, and the lower tract extends from the trachea to the lungs. Although all sites are amenable to cytological sampling, the lower tract is usually the target for the detection of infections, benign lesions, and neoplastic processes. Various sampling techniques are utilized, occasionally with the use of concurrent needle core biopsies (NCB). In this chapter only the lower respiratory tract will be addressed.

Lung cancer is the most common malignancy in the United States, and malignancies from other sites of the body frequently metastasize to the lung. In addition, the increased utilization of radiologic studies over time has led to a corresponding increase in the discovery of incidental long lesions (“incidentalomas”). The advent of ultrasound-guided bronchoscopy and, more recently, navigational bronchoscopy has allowed sampling of these lesions by fine needle aspiration (FNA). In addition, mediastinal lymph nodes may be sampled to determine the presence of metastases and allow staging of the patient by FNA without the need for mediastinoscopy, a more invasive procedure. In patients who are poor surgical candidates, FNA can be used to obtain malignant cells for molecular studies and allowing eligible patients to receive targeted therapies which may extend their lifespan.

The gastrointestinal tract (GIT) comprises of hollow upper and lower tracts, as well as associated solid organs. Cytology of the GIT is performed to detect neoplastic and nonneoplastic lesions and often includes concurrent procurement of needle core biopsies. Sites amenable to cytological sampling include the esophagus, stomach, duodenum, pancreatobiliary, and liver from the upper GIT and the rectum and anus from the lower GIT.

Fine needle aspiration (FNA) is used to triage clinically and radiologically detected thyroid nodules to a specific management, surgery (either total- or hemithyroidectomy), or surveillance. Needle core biopsies of the thyroid are not usually performed, and thus the FNA diagnosis often decides the need for surgery. The most common malignancy of the thyroid is papillary thyroid carcinoma (PTC), and due to its multifocal nature, a diagnosis of malignancy on FNA typically results in a total thyroidectomy. A benign diagnosis is reassuring and allows the patient to avoid surgery and undergo surveillance. Most laboratories report thyroid FNA diagnoses according to “The Bethesda System for Reporting Thyroid Cytology (TBSRTC),” which contains six categories, each with their own rate of malignancy and recommended clinical management (Table 7.1) [1]. Molecular tests are now commonly performed on indeterminate thyroid nodules to help triage patient treatment.