Faculty Bibliography

Background: Fine needle aspiration (FNA) of salivary gland lesions is a fast, minimally invasive and cost-effective procedure that aids in early patient management decisions. Recently, the Milan System for reporting Salivary Gland cytopathology (MSRSGC) was published in order to establish diagnostic categories with implied malignancy risks and recommended clinical follow-up. Our study aims to assess the interobserver reproducibility of salivary gland cytology diagnoses using the MSRSGC.
Design(s): Salivary gland cytology slides from 101 cases with surgical pathology follow-up from 11/2016-06/2019 were blindly and independently reviewed and classified according to the MSRSGC by four cytopathologists. Unweighted and linearly weighted percent agreement and Gwet's AC1 coefficients were calculated in AgreeStat 2015.6/Windows (AgreeStat Analytics).
Result(s): Unweighted percent agreement was 0.69 (substantial agreement) and weighted percent agreement was 0.92 (almost perfect agreement). Unweighted Gwet's AC1 was 0.64 (substantial agreement), and weighted Gwet's AC1 was 0.84 (almost perfect agreement) (Table 1). 50 of 101 (49%) cases had complete agreement among all 4 observers, 77 (76%) had at least 3 observers agreeing on the same diagnosis, and 99 (98%) had at least 2 observers agreeing on the same diagnosis. Category IVA (benign neoplasm) was the most likely to show interobserver agreement: among the 51 cases in which at least 2 cytopathologists agreed on a diagnosis of category IVA, 34 (67%) showed complete agreement among all 4 cytopathologists. Two cases showed no agreement among any observers. One low-grade mucoepidermoid carcinoma had MSRSGC diagnoses ranging from I to IVB, and one secretory carcinoma had MSRSGC diagnoses ranging from III to VI. Low-grade mucoepidermoid carcinoma is reportedly the most common malignant salivary gland tumor associated with false-negative diagnoses on cytology and is often misdiagnosed as a pleomorphic adenoma, due to the presence of bland-appearing intermediate cells as well as confusion between mucin and chondromyxoid stroma (Figure 1). The case of secretory carcinoma showed scant cellularity on cytology, confounding an accurate diagnosis (Figure 2).
Conclusion(s): Interobserver reliability analyses using the MSRSGC showed substantial to almost perfect agreement among the four observers in our study. Only two cases showed no agreement. Category IVA (benign neoplasm) is the most likely to show complete agreement among all observers

Introduction: Recent studies evaluating p16 immunohistochemistry (IHC) in cell blocks (CB) of fine needle aspirations (FNAs) in patients with oropharyngeal squamous cell carcinoma (OP-SCC) have shown good correlation between cytology and surgical pathology. Our study aimed to determine the reproducibility of p16 IHC scoring in CBs. Additionally, we evaluated whether interobserver variability would significantly affect the optimal threshold for p16 IHC positivity in CBs.
Material(s) and Method(s): 40 FNAs from 2014-2019 of head and neck squamous cell carcinoma with p16 IHC were obtained. Surgical pathology p16 IHC results were set as reference. p16 IHC stained CBs were scored independently by 5 cytopathologists and recorded as percentage of tumor cell positivity: 0%,0-1%,1-10%,10-50%,50-70%,70%. AgreeStat2015.6/Windows software was used to calculate the percent agreement (Pa) and Gwet's AC1 statistic to assess inter-rater reliability. ROC curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values (IBM SPSS version 25).
Result(s): Overall performances of the raters were similar, with areas under the curve (AUCs) ranging from 0.88-0.95 (Figure 1). >10% appeared to be the optimal threshold for p16 positivity because this was the lowest threshold to reach 100% specificity with high sensitivity (55-84%) in all 5 raters. Using the >10% as threshold, the Pa was 86% (95% CI 0.78-0.94) and Gwet's AC1 coefficient was 0.72 (95% CI 0.56-0.89).
Conclusion(s): While the goal in developing guidelines for the interpretation of p16 IHC on cytology CBs is to provide generalizable standards for all cytopathologists, interobserver variability must be taken into account. Prior studies have shown optimal cutoffs ranging from >0% (any staining) to >70%, with sensitivity and specificity values ranging from 37%-100%. While our study did not show perfect agreement, all cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold with a percent agreement of 86%. [Formula presented]
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Background: HPV-related oropharyngeal squamous cell carcinoma (OP-SCC) has a superior prognosis and response to therapy than that of conventional head-and neck SCC (HNSCC). The College of American Pathologists (CAP) guidelines recommend that P16 immunostaining (IHC) in >70% of tumor cells is an excellent surrogate marker for HPV in surgical pathology OP-SCC. Fine needle aspiration (FNA) cytology is an ideal method for obtaining diagnostic material for OP-SCC and may represent the only attainable specimen. However, there is no consensus for interpretation of P16 IHC result in cytology preparations. Our study aims to assess OP-SCC P16 staining in cell block cytology preparations in comparison with P16 staining on surgical pathology specimens.
Design(s): FNA specimens from 2014-2019 of OP-SCC with P16 IHC staining were obtained. Surgical pathology P16 IHC results were set as the gold standard. Cytology cell block tumor cellularity (<100 vs >100 cells) and P16 percentage of tumor cell positivity (0%, 1-10%, 11- 50%, 51-70%, and >70%) were recorded. Using different threshold levels of P16 tumor cell positivity in cell blocks as compared with surgical P16 IHC results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.
Result(s): 40 matched FNA neck lymph node/mass cytology and surgical cases were identified. Sensitivities and specificities varied when thresholds changed, with sensitivities and specificities ranging from 93.5% and 66.7% (respectively) when any P16 positivity is seen (>0%), to 56.7% and 100% (respectively) when P16 positive threshold is set at >70% (table 1 and figure 1). <100 and >100 tumor cells were seen in 11 and 29 cases respectively. (Table presented)
Conclusion(s): Our study shows that P16 IHC performed on cytology cell blocks can serve as a surrogate marker for the detection of HPV, similar to P16 staining in surgical pathology, with high sensitivity and specificity levels. The challenge in cytology specimens is choosing the proper threshold to balance between the optimal sensitivity and specificity. Our data suggests that using a threshold lower than that of surgical pathology (70%) for p16 positivity may be appropriate for FNA specimens, as lower thresholds displayed increased sensitivities with only moderately lower specificities. Of note out of the 11 cases with <100 tumor cells, only one cases was a false negative, indicating that tumor cellularity may not affect P16 interpretation on cell block

Background: Diagnosis of microinvasion (MI) in breast core needle biopsy (CNB) can be challenging particularly in a background of carcinoma in situ (CIS) involving sclerosing lesion with periductal fibrosis and lymphocytic infiltrate. Immunohistochemical stains (IHC) for myoepithelial cells aid in confirming MI. Surgical management of MI deviates from CIS as the former includes sentinel lymph node biopsy (SLNB) while the latter typically includes SLNB only when total mastectomy (TM) is planned. We investigated the utility of IHC in diagnosing MI in our CNBs and its impact on final histopathology on surgical excision.
Design(s): We conducted a search for cases of CIS with foci suspicious for MI, in which IHC for calponin and p63 was used to confirm MI (defined as invasive carcinoma <=1 mm) between January 2010 and June 2019. CIS included ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). MI cases diagnosed based on routine histology were also collected for the same time period. Only cases with follow up excision data were included. Cases with synchronous invasive carcinoma were excluded. Clinicopathologic data including age, size, laterality, resection type, SLNB status and biomarker profiles were compared. Graphpad Prism software was used for statistical analysis.
Result(s): We identified 106 cases of CIS (102 DCIS, 4 LCIS), where IHC was used to confirm MI (MI-IHC hereafter). Mean age was 58 years. Of the 106 cases MI-IHC was identified in 24 cases (23%). See table. All 24 MI-IHC cases had SLNB (100%). Of the 82 CIS cases, 39 had SLNB (48%). Relative risk of finding invasive carcinoma/MI on resection in MI-IHC was 1.8 (p=0.03) compared to CIS. There was no correlation between the biomarker profile with the resection outcome in either CIS (p=0.5, Fisher's exact test) or MI-IHC cases (p=3.4, Chi-square test). We identified 7 cases of MI, diagnosed on routine histology without IHC, of which 5 (71%) had invasive carcinoma/MI and 2 (29%) had CIS or no residual carcinoma on resection. Mean size of invasive carcinoma and CIS on resection in this group was 11 mm and 25 mm, respectively. The resection outcome between MI-IHC and MI based on routine histology was not significant (p=0.6). (Table presented)
Conclusion(s): IHC helped diagnose MI in CNB for CIS in 23% of cases. Compared to CIS, the diagnosis of MI-IHC carried a relative risk of 1.8 in finding invasive carcinoma/MI on resection. There was no difference in the significance of the method used for the diagnosis of MI

Background: Salivary gland neoplasms are rare and the majority are benign with only 20% displaying malignancy. Fine needle aspiration (FNA) plays an essential role in the initial evaluation of salivary gland lesions by providing a pre-operative diagnosis to determine appropriate management. Recently, a tiered classification system known as the Milan System for reporting Salivary Gland cytopathology (MSRSGC) has been published. This system formalizes diagnostic categories with related malignancy risk, recommended clinical therapy and follow-up. Our study aims to compare sensitivity, specificity and risk of malignancy (ROM) between the MSRSGC and the original FNA cytology diagnostic categories used at our institution to determine if the MSRSGC offers added benefit.
Design(s): Salivary gland cytology slides from subjects with final surgical pathology resections from 11/2016-06/2019 were blindly reviewed and classified according to the MSRSGC. MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared to the original cytology diagnostic categories. Sensitivity, specificity and ROM of diagnostic categories were calculated for both systems.
Result(s): Follow-up histopathology was available for 101 patients with salivary gland lesions. The MSRSGC had a sensitivity of 69.0% and a specificity of 92.9%. The original classification system had a sensitivity of 75.0% and a specificity of 89.9%. ROM for MSRSGC categories and original diagnostic categories are given in Table 1 and listed side by side to reflect distribution of cases in each system. (Table presented)
Conclusion(s): Performance of the MSRSGC was comparable to that of the original classification system in the majority of cases. Both systems had a similar sensitivity, specificity and ROM in the equivalent categories. The single "non-diagnostic" and the three "nonneoplastic" cases under MSRSGC that showed histopathologic evidence of malignancy were called "negative for malignancy" in the original classification showing lack of cytohistologic correlation for both systems due to sampling errors. Two of the three cases classified as "atypia of undetermined significance" under the MSRSGC were originally classified as "negative for malignancy". Our findings suggest that traditional diagnostic classification methods for salivary gland cytopathology already established at an institution can perform as well as the MSRSGC in relaying the appropriate diagnostic information, undermining the need for transition to a new classification system

Breast MRI is the most sensitive imaging modality for assessment of the nipple-areola complex (NAC), which is important both in cancer staging and in high-risk screening. However, the normal appearance of the nipple at MRI is not well defined because of a paucity of scientific literature on this topic. Hence, there is a lack of descriptive terminology and diagnostic criteria, which may account for the wide variability in interpretation among radiologists when assessing the NAC on MR images. In light of the current shift toward possible expanded use of abbreviated (ie, fast) breast MRI for screening in women at average risk for cancer in particular, and because an increasing number of women now undergo nipple-sparing mastectomy for therapeutic and/or prophylactic indications, careful assessment of the NAC at MRI is essential. In this article, the normal pattern of nipple enhancement at MRI is defined on the basis of findings observed in healthy individuals, normal nipple enhancement at MRI is correlated with the structural anatomy of the nipple at histopathologic analysis, and artifacts and pitfalls related to MRI of the NAC are reviewed. Understanding the normal range of nipple morphology and enhancement at MRI is important, as it enables radiologists to better differentiate between normal and abnormal nipple findings with increased diagnostic confidence. ^©RSNA, 2018 See discussion on this article by Cohen and Holbrook .

OBJECTIVE:Because of the indolent nature of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP) and potential requisite for conservative treatment, it is crucial to identify features of this entity pre-operatively. Our group recently published our findings that there are several cytomorphologic features that may be used as clues to distinguish NIFTP, PTC and follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we aimed to determine the interobserver reproducibility of these findings. METHODS:Pre-surgical FNA slides from NIFTP (n=30), classic PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blindly. Presence of selected cytomorphologic features was recorded and compared to determine percent agreement and inter-rater reliability among study cytopathologists using Gwet's AC1 statistics. RESULTS:For all the cytomorphologic features, the overall percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's AC1 0.30 to 0.80). There was substantial or almost perfect agreement (Gwet's AC1 >0.60) in seven cytomorphologic features in the classic PTC group, in six features in the NIFTP group, and in five features in the FA group. There were no features with poor agreement (Gwet's AC1<0.0). CONCLUSIONS:The current study supports the reproducibility of our previous findings. The high level of agreement amongst pathologists for these groups, and particularly the NIFTP group, supports the notion that when viewed in combination as a cytologic profile, these cytomorphologic features may assist the cytopathologist in raising the possibility of NIFTP pre-operatively. This can potentially aid clinicians in deciding whether more conservative treatment may be appropriate.

Introduction: Because of the indolent nature and potentially conservative treatment of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP)- an entity recently removed from the malignant papillary thyroid carcinoma (PTC) category, it is crucial to identify features of this entity pre-operatively. Our group has recently published our findings that several statistically significant associations appear to be present between cytomorphologic features and surgical diagnosis that may be used as clues to distinguish NIFTP, PTC and follicular adenoma (FA) on fine-needle aspiration (FNA). Therefore, we set out to determine the reproducibility of these results. Materials and Methods: Pre-surgical FNA slides from NIFTP (n=30), classical PTC (n=30) and FA (n=30) collected from 1/2013-8/2016 were reviewed by 7 cytopathologists blind and independently. Presence of cytomorphologic features was recorded and compared to determine concordance amongst cytopathologists. For each feature, the concordance was compared between NIFTP, PTC and FA by Fisher's Exact Test. Utilizing the majority consensus for presence or absence of each cytomorphologic feature, differences amongst NIFTP, PTC and FA presurgical FNAs were assessed for each feature by Fisher's Exact Test. Results: For all the cytomorphologic features, the concordance rates amongst the pathologists ranged between 78 to 93%. The concordance rates were similar between the NIFTP, PTC and FA groups (Table 1). Comparing each cytomorphologic feature (present/absent determined by majority consensus) amongst the NIFTP, PTC and FA groups displayed statistically significant differences for all features (Table 2). Conclusions: The current study supports our previous findings that there are cytomorphologic differences between the three surgical pathology groups-NIFTP, PTC and FA, and shows that these results are reproducible. The presence or absence of each feature viewed in combination as a profile may assist the cytopathologist in raising the possibility of NIFTP pre-operatively, potentially aiding clinicians in deciding whether a more conservative treatment plan is appropriate. (Table Presented)

The breast is an unusual site for carcinoid metastasis. Due to increasing survival rates for carcinoid tumors, however, awareness of their rare complications is important. Carcinoid metastasis to the breast typically presents as a palpable breast mass or a mass on screening mammogram. Because imaging findings are nonspecific, the diagnosis is established through histological findings of neuroendocrine features corresponding with the known primary carcinoid pathology. Correctly distinguishing metastatic carcinoid from primary breast carcinoma is crucial to avoid more invasive procedures required for the latter. Two cases of metastatic carcinoid to the breast are presented with review of the literature.

Polyacrylamide gel (PAAG) injection remains an uncommon method of breast augmentation. Providers must recognize the clinical and radiological manifestations to optimize management. The clinical and radiological findings of PAAG injection may mimic malignancy and silicone breast augmentation. We described two patients with prior PAAG breast augmentation with physical exam and imaging findings concerning for malignancy. We reviewed the literature on PAAG breast augmentation and compare PAAG to silicone breast augmentation. The management of such patients is discussed.