Madelyn Lew

Young investigator challenge: The utility of GATA3 immunohistochemistry in the evaluation of metastatic breast carcinomas in malignant effusions.

It is not uncommon to encounter challenges in the immunohistochemical confirmation of metastatic breast cancer given the limited sensitivities of mammaglobin and gross cystic disease fluid protein 15 (GCDFP‐15/BRST‐2) and the significant proportion of triple‐negative breast carcinomas (ie, tumors that are negative for estrogen receptor [ER], and progesterone receptor [PgR], and human epidermal growth factor 2 [HER2]). GATA binding protein 3 (GATA3) has emerged as a potentially useful immunohistochemical adjunct during the evaluation of metastatic breast carcinomas in cytology specimens. The objective of the current study was to examine GATA3 expression in the context of malignant effusions secondary to both mammary and extramammary malignancies.

Implementing noninvasive follicular thyroid neoplasm with papillary-like nuclear features may potentially impact the risk of malignancy for thyroid nodules categorized as AUS/FLUS and FN/SFN

Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC) has recently been reclassified as noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP). Implementation of the new terminology may alter the implied risk of malignancy (ROM) across the six categories of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC).

Implication of Suspicious Cytology in Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Pancreatic Cancer

PurposeEndoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has become a preferred technique to evaluate pancreatic masses. The clinical management of a “suspicious for adenocarcinoma” cytological diagnosis is unclear in unresectable cases. We sought to determine whether a suspicious diagnosis in the setting of a high clinical suspicion of malignancy could be sufficient for initiating non-operative therapy, such as chemotherapy, in unresectable patients.MethodsTwenty-nine solid pancreatic mass cytology specimens obtained by EUS-FNA with a diagnosis of suspicious for adenocarcinoma were identified from 2000 to 2012. Pathology, clinical, and radiologic data were analyzed.ResultsAdditional procedures were performed in 21 of the 29 patients. Sixteen of the 21 patients had confirmation of malignancy on further tissue sampling and an additional 2 had confirmed unresectable cancers during surgical exploration. Three of the 21 patients had benign diagnoses on subsequent tissue sampling. Of the remaining eight patients who did not undergo additional diagnostic procedures, six were deemed clinically malignant and treated, one died within a year of the EUS-FNA, and one was lost to follow-up.ConclusionsConsideration of a suspicious diagnosis on EUS-FNA of solid pancreatic masses as sufficient for initiating non-operative therapy is reasonable in the setting of a high clinical suspicion of malignancy.

Cytologic Features and Immunocytochemical Profiles of Malignant Effusions with Metastatic Papillary Thyroid Carcinoma: A Case Series from a Single Institution

Objective: Malignant effusions due to papillary thyroid carcinoma (PTC) are rare, but portend a poor prognosis. PTC metastases, although rare, most frequently occur in the lungs and bone. Therefore, differentiating thyroid etiology of malignant effusions from other sites becomes clinically significant in patient management. This study examines morphologic and immunocytochemical findings in 5 cases of malignant effusions with PTC involvement. Study Design: The electronic database at the University of Michigan was searched from January 1, 1995 to December 31, 2014 for malignant pleural effusions with PTC involvement. Clinicopathologic data were obtained from electronic medical records. Cytologic slides were reviewed. Results: Five cases of malignant effusions due to PTC were identified. Characteristic cytologic features of PTC, including ovoid nuclei, irregular nuclear contours, and psammomatous calcifications, were seen. However, the predominant cytologic feature observed was moderate amounts of delicate to vacuolated cytoplasm within the tumor cells. A review of immunocytochemistry demonstrated that all 5 cases showed patchy to diffuse TTF-1 positivity and diffuse positivity for Pax-8. Thyroglobulin only showed focal to patchy positivity in 3 of 5 cases. Conclusion: Given the morphologic features found in our case series, an immunocytochemical workup for the evaluation of involvement of an effusion by a thyroid primary is crucial for accurate diagnosis and appropriate clinical treatment.

Cytologic and immunohistochemical evaluation of low-grade spindle cell lesions of the gastrointestinal tract

Spindle cell lesions of the gastrointestinal tract are relatively uncommon compared with the frequency of their epithelial counterparts. Although gastrointestinal stromal tumors and leiomyomas are the most commonly encountered spindle cell lesions in the stomach and esophagus, respectively, there are other less common diagnostic entities that should be considered for accurate diagnoses as well as appropriate patient treatment and clinical follow-up. Given the morphologic overlap of low-grade spindle cell lesions on cytologic preparations, ancillary studies play a key role in differentiating these lesions from one another.

Comparative study of TERT promoter mutation status within spatially, temporally and morphologically distinct components of urothelial carcinoma

Telomerase reverse transcriptase (TERT) is a ribonucleoprotein involved in maintaining the length of telomeres. In the absence of TERT expression, differentiated cells can only divide a finite number of times before undergoing cellular senescence – often referred to as the Hayflick limit. Mutations within the promoter region of TERT that create consensus binding sequences for ETS family transcription factors are a common mechanism by which neoplastic cells increase TERT expression and overcome this limit [1]. TERT promoter mutations are common in many cancer types including 60-80% of urothelial carcinomas (UC) [2,3]. Given the high frequency of these mutations in UC and absence of these mutations in non-neoplastic/benign mimics of UC [4], TERT promoter mutations may serve as potential biomarker for monitoring patients with a history of malignancy. This article is protected by copyright. All rights reserved.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37‐year‐old female with a history of metastatic ductal carcinoma of the breast (modified Bloom‐Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly‐shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA‐3 (+), ER (+), PAX‐8 (−), and TTF‐1 (−) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA‐3, hormonal marker(s), PAX‐8, and TTF‐1, may be useful in some cases. GATA‐3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530–534.

The Undergraduate Training in Genomics (UTRIG) Initiative: Early & active training for physicians in the genomic medicine era

Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIGs collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

Retinal pigment epithelium adenoma in vitreous fluid cytology

Ocular cytology specimens are relatively uncommon, adding to the difficulty of their evaluation by cytopathologists. While melanomas account for a majority of primary intraocular pigmented lesions, other diagnostic considerations must be included in the differential. This brief report highlights a case of a pigmented ocular lesion in a 24‐year‐old man and key morphologic, immunohistochemical, and clinical differences between melanoma, melanocytoma, choroidal nevus, and retinal pigment epithelium (RPE) adenoma.