Richard M. DeMay

Cytopathology of false negatives preceding cervical carcinoma

The Papanicolaou smear has been a remarkably effective tool in cancer prevention, but it is not a perfect test. Although the most important factor in failure of cervical cancer prevention is lack of adequate screening, other factors include problems with sampling, interpretation, and effective clinical follow-up. A small number of rapidly developing cervical cancers probably also arise in the interval between Papanicolaou smear screenings. Consequently, cervical cancer will develop in some women despite appropriate screening. This article will analyze some of the problems relating to diagnostic errors, which include abnormal cells that are few (< 100), small, or bland.

Continuous Exposure to Chrysotile Asbestos Can Cause Transformation of Human Mesothelial Cells via HMGB1 and TNF-α Signaling

Malignant mesothelioma is strongly associated with asbestos exposure. Among asbestos fibers, crocidolite is considered the most and chrysotile the least oncogenic. Chrysotile accounts for more than 90% of the asbestos used worldwide, but its capacity to induce malignant mesothelioma is still debated. We found that chrysotile and crocidolite exposures have similar effects on human mesothelial cells. Morphological and molecular alterations suggestive of epithelial-mesenchymal transition, such as E-cadherin down-regulation and β-catenin phosphorylation followed by nuclear translocation, were induced by both chrysotile and crocidolite. Gene expression profiling revealed high-mobility group box-1 protein (HMGB1) as a key regulator of the transcriptional alterations induced by both types of asbestos. Crocidolite and chrysotile induced differential expression of 438 out of 28,869 genes interrogated by oligonucleotide microarrays. Out of these 438 genes, 57 were associated with inflammatory and immune response and cancer, and 14 were HMGB1 targeted genes. Crocidolite-induced gene alterations were sustained, whereas chrysotile-induced gene alterations returned to background levels within 5 weeks. Similarly, HMGB1 release in vivo progressively increased for 10 or more weeks after crocidolite exposure, but returned to background levels within 8 weeks after chrysotile exposure. Continuous administration of chrysotile was required for sustained high serum levels of HMGB1. These data support the hypothesis that differences in biopersistence influence the biological activities of these two asbestos fibers.

Benign cystic mesothelioma involving the female genital tract: Report of four cases

Four cases of benign cystic mesothelioma are described. The disease affects young white women (mean age, 30 years), and they present with chronic pelvic pain. At laparoscopy or laparotomy, multiple cysts ranging in size from 0.5 to 4 cm in diameter and containing clear fluid are seen. The disease commonly affects the pelvic organs and/or omentum. With the electron microscope, the cell of origin of this proliferative process is shown to be the mesothelial cell. The disease has been previously described under a variety of terms. There seems to be a tendency for recurrence, but no malignant potential is apparent. Treatment may be conservative with preservation of pelvic organs. Benign cystic mesothelioma should be considered in the differential diagnosis of cystic lesions of the female genital tract.

Follicular lesions of the thyroid: A retrospective study of 1,348 fine needle aspiration biopsies

Fine needle aspiration (FNA) has proven to be an effective tool in management of patients with thyroid nodules. However, the diagnosis of follicular patterned lesions can be challenging. The surgical and cytopathology computer database at a large referral medical center was searched for cases that had both cytologic and histologic thyroid accessions from January 2004 to November 2008. A total of 1,255 histologic thyroid specimens and 2,776 thyroid FNA biopsies were retrieved for review. Histologically, 272 overt malignancies were identified; 20 (7.4%) were follicular carcinomas. Cytologically, 1,348 cases were follicular‐patterned lesions, comprising 1,044 cases of “benign follicular nodules” (BFN), 137 cases of “follicular lesions of undetermined significance” (FLUS), and 167 cases of “suspicious for follicular neoplasm” (SFN). Seventy‐nine (7.5%) of BFN, 23 (16.8%) of FLUS, and 65 (38.9%) of SFN cases had histologic follow‐up. Overt malignancy, a cystic papillary carcinoma, was identified histologically in only one case of BFN, for a negative predictive value of 98.7%. Overt malignancy was identified histologically in two cases of FLUS, both follicular variant of papillary carcinoma, for a positive predictive value of 8.7%. Overt malignancy was identified histologically in 14 cases of SFN, for a positive predictive value of 21.5%. Five follicular carcinomas were identified histologically in the SFN category, all minimally invasive. Incidental (“occult”) papillary microcarcinoma were identified histologically in all three categories. In this study, the risk of overt malignancy increases from 1.3%, to 8.7%, to 21.5% for BFN, FLUS, and SFN, respectively. All follicular carcinomas identified histologically occurred in the SFN category and all were minimally invasive. Papillary microcarcinomas can occur in any of the three diagnostic categories. Diagn. Cytopathol. 2012;40:E8–E12.

Hurthle cell variant of papillary carcinoma of the thyroid gland.

T h e histogenesis and clinical significance of Hurthle cells associated with thyroid gland neoplasia are uncertain. The following case demonstrates the unusual occurrence of a papillary carcinoma, composed entirely of Hurthle cells. This case supports the contention that Hurthle cells may develop as part of the natural history of any thyroid neoplasm. Thyroid carcinoma associated with Hurthle cells may not be a separate clinicopathologic entity, although the effect of this association on biologic behavior is uncertain.

Fine needle aspiration cytology of the oxyphil variant of papillary carcinoma of the thyroid : A report of three cases

BACKGROUND A number of histologic variants of papillary carcinoma of the thyroid have been described, including an oxyphil cell subtype (OVPC). Few OVPC cases have been detailed cytologically. CASES Smears prepared from aspiration biopsies, as well as the corresponding histologic sections and clinical histories, were reviewed for three cases. Two patients had asymptomatic thyroid tumors, and the third developed neck tumors after thyroid cancer surgery. All smears revealed scattered papillary groups and monolayered sheets. The large, neoplastic cells had abundant, granular cytoplasm and eccentrically placed nuclei. Nuclear grooves and intranuclear inclusions were variably present. Psammoma bodies and colloid were not identified. Histologically the tumors consisted predominantly of oxyphil cells arranged in papillary patterns and with nuclear features of usual papillary carcinoma (UPC). CONCLUSION OVPC can be diagnosed in smears composed predominantly of large oxyphil cells but showing features associated with UPC and can be cytologically distinguished from follicular oxyphilic tumors and UPC.

How to write an article: Preparing a publishable manuscript!

Most of the scientific work presented as abstracts (platforms and posters) at various conferences have the potential to be published as articles in peer-reviewed journals. This DIY (Do It Yourself) article on how to achieve that goal is an extension of the symposium presented at the 36th European Congress of Cytology, Istanbul, Turkey (presentation available on net at http://alturl.com/q6bfp). The criteria for manuscript authorship should be based on the ICMJE (International Committee of Medical Journal Editors) Uniform Requirements for Manuscripts. The next step is to choose the appropriate journal to submit the manuscript and review the ‘Instructions to the authors’ for that journal. Although initially it may appear to be an insurmountable task, diligent organizational discipline with a little patience and perseverance with input from mentors should lead to the preparation of a nearly perfect publishable manuscript even by a novice. Ultimately, the published article is an excellent track record of academic productivity with contribution to the general public good by encouraging the exchange of experience and innovation. It is a highly rewarding conduit to the personal success and growth leading to the collective achievement of continued scientific progress. Recent emergences of journals and publishers offering the platform and opportunity to publish under an open access charter provides the opportunity for authors to protect their copyright from being lost to conventional publishers. Publishing your work on this open platform is the most rewarding mission and is the recommended option in the current modern era. [This open access article can be linked (copy-paste link from HTML version of this article) or reproduced FREELY if original reference details are prominently identifiable].

Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla: Two case reports with review of literature

Mixed adenoneuroendocrine carcinoma (MANEC) of ampulla is rare, with only 13 cases reported, and the diagnoses were all based on histology mostly after surgery. We describe two new cases with cytological features of signet ring‐cell carcinoma mixed with small‐cell carcinoma, and intestinal adenocarcinoma mixed with large‐cell neuroendocrine carcinoma. Our cases and literature review demonstrate the higher frequency of periampullary‐duodenum subtype in MANEC compared with non‐MANEC ampullary carcinomas. In accordance, of the 14 MANEC cases with detailed morphology available, the most common glandular components are intestinal‐type carcinoma (6/14), followed by goblet carcinoid tumor (3/14), signet ring‐cell carcinoma (2/14), pancreatobiliary‐type carcinoma (2/14), and pancreatic acinar cell carcinoma (1/14). The intestinal‐type carcinoma and goblet carcinoid in MANEC are favorable histological types showing no distant metastasis or mortality (0/9) during 6–36 months follow‐up. In contrast, the signet ring cell, pancreatobiliary‐type carcinoma, and acinar cell carcinoma are unfavorable with distant metastatic rate and mortality rate of 80% (4/5) during 3–16 months follow‐up. The combination of favorable glandular histological types with high‐grade neuroendocrine tumors (neuroendocrine carcinoma) has a mortality rate of 0% (0/3), whereas the combination of unfavorable glandular types with low‐grade neuroendocrine tumors (e.g., carcinoid, atypical carcinoid) has a mortality rate of 100% (3/3). In addition, younger age (<40 years) seems to be associated with high mortality rate of 100% (2/2). Overall, cytology preparations are able to make the diagnosis of MANEC and distinguish the subcomponents. Disease progression is apparently driven by the carcinomatous component of the tumor. Diagn. Cytopathol. 2014;42:1075–1084.

Follicular Neoplasm/Suspicious for a Follicular Neoplasm

The 1st edition of the Bethesda System for Reporting Thyroid Cytopathology introduced six categories for reporting fine needle aspiration results, one of which was termed “follicular neoplasm (FN)” or “suspicious for a follicular neoplasm (SFN).” These are synonymous terms for the same category, and it is recommended that a laboratory chooses the term it prefers and use it exclusively for nodules that are suspicious for a follicular neoplasm. The criteria proposed in the 1st edition are reaffirmed in this 2nd edition: this category is intended for those aspirates that are at least moderately cellular and comprised of follicular cells, most of which show significant architectural abnormality in the form of microfollicles and/or trabeculae. In this 2nd edition, the criteria have been expanded, however, to include follicular-patterned aspirates with mild nuclear changes (mild enlargement, contour irregularity, and clearing); such cases can be classified as FN/SFN so long as true papillae and intranuclear pseudoinclusions are absent. In such cases, a note that some nuclear features raise the possibility of an invasive follicular variant of papillary carcinoma or the more indolent noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) can be helpful. The recommended management of a patient with a diagnosis of FN/SFN is surgical excision of the lesion, most often a hemithyroidectomy or lobectomy; molecular testing may be used to supplement risk assessment in lieu of proceeding directly to surgery.

Compensation crisis related to the onsite adequacy evaluation during FNA procedures-Urgent proactive input from cytopathology community is critical to establish appropriate reimbursement for CPT code 88172 (or its new counterpart if introduced in the future)

The confusion centered around appropriate use of the CPT billing code 88172 is addressed in the commentary from the Economic and Government Affairs Committee of the American Society of Cytopathology (ASC) who have written a timely commentary in this issue of Cytojournal, “Adequate Reimbursement is Crucial to Support Cost-Effective Rapid Onsite Cytopathology Evaluations”. Currently, lack of standardized use within and between pathology departments is stirring unhealthy practices of denying reimbursements for this critical and legitimate cytopathology service. This editorial discusses the important concerns raised in this commentary and recommends immediate corrective action. (See also Al-Abbadi MA, et al. Adequate reimbursement is crucial to support cost-effective rapid on-site cytopathology evaluations. CytoJournal 2010;7:22)