Christopher VandenBussche

Impact of reclassifying noninvasive follicular variant of papillary thyroid carcinoma on the risk of malignancy in The Bethesda System for Reporting Thyroid Cytopathology.

Recent discussions have focused on redefining noninvasive follicular variant of papillary thyroid carcinoma (NI‐FVPTC) as a neoplasm rather than a carcinoma. This study assesses the potential impact of such a reclassification on the implied risk of malignancy (ROM) for the diagnostic categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).

The Johns Hopkins Hospital template for urologic cytology samples: parts II and III: improving the predictability of indeterminate results in urinary cytologic samples: an outcomes and cytomorphologic study.

Urine cytology represents a major portion of testing volume in many cytopathology laboratories.

A review of reporting systems and terminology for urine cytology

Urine cytology continues to play an important role in the diagnosis and management of urothelial carcinoma, a common cancer of adults with significant morbidity and mortality. Because of its high sensitivity for high‐grade urothelial tumors, including lesions that may be cystoscopically occult, urine cytology nicely compliments cystoscopic examination, a method that detects most low‐grade tumors. Over the decades, several reporting schemes for urine cytology have been published in the literature, each of which has relative strengths and weaknesses. Unlike cervical cytology, there has not been widespread acceptance and use of any particular reporting scheme for urine cytology studies. Thus, terminology and criteria for urine cytology reporting are not uniform among pathologists, which can frustrate clinicians and hinders interlaboratory comparisons. Cancer (Cancer Cytopathol) 2013;121:9–14

The Johns Hopkins Hospital template for urologic cytology samples: part I-creating the template.

The most important indicator for urologic surgeons at The Johns Hopkins Hospital to have a patient undergo cystoscopy is a cytologic diagnosis of high‐grade urothelial carcinoma. The template was designed to standardize diagnostic categories so clinicians can manage their patients uniformly. The template was based in part on the Bethesda System for cervical cytology.

Borderline atypical ductal hyperplasia/low-grade ductal carcinoma in situ on breast needle core biopsy should be managed conservatively.

The differential diagnosis of low–nuclear grade intraductal epithelial proliferations of the breast includes atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). This distinction can be difficult on core needle biopsy (CNB) but can have significant clinical ramifications. We examined the clinical course of patients diagnosed on CNB with borderline ADH/DCIS lesions [marked ADH (MADH)] at our institution. A total of 74 patients were diagnosed with MADH on CNB and underwent an excisional biopsy (EB). The majority of these CNBs reviewed at outside hospitals had been classified as DCIS. Twenty patients (27%) had benign findings or lobular neoplasia in their EB, 18 (24%) had ADH, 33 (45%) had DCIS, and 3 (4%) had DCIS and invasive ductal carcinoma (IDC). Among the 38 patients who were not diagnosed with DCIS or IDC on EB, no patient underwent further surgery or radiation postoperatively. Thirty-seven of these 38 patients had no recurrences, whereas 1 patient developed a “recurrence” that on our review was likely residual localized MADH. The mean follow-up for these patients was 54 months. Of the 36 patients diagnosed with DCIS or IDC on EB, <20% required mastectomy. On review, MADH involving an intermediate-sized duct on CNB and the amount of residual lesion on imaging was significantly associated with DCIS or IDC on EB. Conversely, MADH involving columnar cell lesions and the presence of calcification on CNB were significantly associated with benign pathology on EB. In conclusion, our study provides preliminary data that justify a conservative approach to borderline ADH/DCIS lesions on CNB: that is, diagnose as MADH and treat by conservative excision.

Can the Tall Cell Variant of Papillary Thyroid Carcinoma Be Distinguished from the Conventional Type in Fine Needle Aspirates? A Cytomorphologic Study with Assessment of Diagnostic Accuracy

Objectives: The tall cell variant of papillary thyroid carcinoma (TCV-PTC) is an aggressive variant of PTC requiring accurate cytopathologic diagnosis for early aggressive management. Study Design: Twenty-five cases of TCV-PTC in which the tall cells comprised at least 30% of surgically resected tumor were included in the study. The direct smears from a preoperative fine needle aspiration (FNA) and available hematoxylin and eosin cell block sections were reviewed. Ten cases of TCV-PTC were randomly selected and blinded with an equal number of conventional PTC cases. Representative slides were independently reviewed by 7 cytologists. Results: In a majority of the cases, the FNA direct smears were hypercellular and displayed flat monolayer sheets of cells. Tall columnar cells with cytoplasmic tails were seen in 56% of cases. The presence of large polygonal follicular cells with abundant granular oncocytic cytoplasm and distinct cell borders was the most common feature seen in all cases. Seventeen (68%) cases displayed intranuclear pseudoinclusions in cells with abundant granular cytoplasm. A correct diagnosis of TCV-PTC was made in 30-40% of cases by 7 study participants. Conclusions: The correct recognition of TCV-PTC features in preoperative FNA is important for clinical management, and reporting these features in a cytopathology report is suggested.

Benign-appearing urothelial tissue fragments in noninstrumented voided urine specimens are associated with low rates of urothelial neoplasia.

The presence of urothelial tissue fragments (UTF) in voided urine (VU) is often considered an abnormal finding that may be associated with the presence of urothelial papillary neoplasms. In the current study, the authors reviewed VU specimens containing benign‐appearing UTF (BUTF) to determine the associated rate of urothelial neoplasia at the study institution.

Clinicopathologic features of ductal carcinoma in situ in young women with an emphasis on molecular subtype.

Young women with ductal carcinoma in situ treated by breast-conserving therapy have a higher recurrence rate than do older women, and a younger age at diagnosis is associated with worse overall survival after recurrence. This study explores the clinical, pathologic, and immunohistochemical characteristics of ductal carcinoma in situ lesions diagnosed in women 40 years and younger with a focus on molecular subtypes to elucidate features that may contribute to the purported worse outcome for this patient population. Forty-one patients diagnosed with ductal carcinoma in situ at age 40 years and younger were identified over a 10-year period; 31 cases were used to construct tissue microarrays. The microarrays were labeled with antibodies to estrogen receptor, progesterone receptor, HER2, Ki-67, CK5/6, epidermal growth factor receptor, and p53 and subsequently classified as luminal A, luminal B, HER2, basal-like, or unclassifiable triple negative. All patients had high-grade (73.2%) or intermediate-grade (26.8%) ductal carcinoma in situ. The molecular subtype breakdown was 61.3% luminal A, 22.6% luminal B, 13% HER2, and 3.1% unclassifiable triple negative. The mean Ki-67 by subtype was 4.2%, 14%, 9.5%, and 50%, respectively. Mastectomy was performed in 33 patients (80%). Eight patients (20%) underwent excisional biopsy without subsequent mastectomy. In addition to a predominance of high-grade lesions, young patients had a high proportion of luminal B subtype, which may contribute to an increased rate of local recurrence in this population. A larger series is necessary to confirm the impact that the molecular subtypes of ductal carcinoma in situ in younger patients might have on outcome.

Atypical urothelial tissue fragments in noninstrumented voided urine specimens are associated with low but significantly higher rates of urothelial neoplasia than benign‐appearing urothelial tissue fragments

The interpretation of urothelial tissue fragments (UTF) in voided urine (VU) specimens is controversial. If UTF contain cytomorphologically atypical cells, the diagnosis often becomes more challenging. The authors previously analyzed the outcome of patients with benign‐appearing UTF in 274 noninstrumented VU specimens. In this retrospective study, noninstrumented VU specimens containing UTF with atypical cytomorphological features (AUTF) were evaluated and compared with the previous results.

Molecular alterations in non-small cell lung carcinomas of the young.

Lung cancer is the leading cause of cancer death in the United States. Gene alterations are significant in lung tumorigenesis, with certain genes (Kristen rat sarcoma viral oncogene homolog (KRAS), epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK], and B-Raf proto-oncogene, serine/threonine kinase (BRAF)) possessing alterations important in the prognosis and treatment of lung adenocarcinoma. Mutation frequencies are affected by different patient factors, such as smoking history, age, and race. Because most lung cancers occur in patients older than age of 50 years, few studies have examined molecular alterations present in these younger patients. The pathology database was searched for patients age of 50 years or younger with non-small cell lung carcinomas (NSCLCs) tested for EGFR, ALK, KRAS, and/or BRAF alterations. A total of 53 cases were identified. The mean patient age was 44.4 years old, and there were 19 men and 34 women. Of the tumors, 11.6% had ALK rearrangements, 25.5% had KRAS mutations, and 20.0% had EGFR mutations. No BRAF mutations were identified in the 28 cases tested. All but 1 (92% [12/13]) tumor with KRAS mutation were from women patients. A smoking history of greater than 5 pack-years was associated with KRAS mutations and negatively associated with EGFR mutations and ALK translocation. The frequencies of EGFR mutation and ALK translocation in the study cohort are greater than the reported frequencies among NSCLC from adults of all ages in the United States but less than the reported frequencies among NSCLC from East Asian young adults. The frequency of KRAS mutation is significantly greater than what was previously found in young Japanese patients.