This report concerns a 71-year-old female with long standing untreated toxic multinodular goiter (TMG) coexisting with anaplastic thyroid carcinoma who presented with progressive shortness of breath and easy fatigability. Thyroid function tests showed suppressed TSH and elevated FT4 and FT3. Anti-thyroid hormone drugs were started. Thyrotropin receptor antibody was negative. A thyroid scan revealed both hot and cold nodules and fine needle aspiration biopsy (FNAB) of the thyroid gland showed colloid nodule. Chest CT scan imaging revealed an enlarged thyroid gland with the right lobe compressing the trachea. Patient underwent total thyroidectomy, final histopathology showed Anaplastic thyroid carcinoma. Our case is interesting from a pathophysiologic perspective,since it suggests that TMG can potentially transform into an aggressive form of thyroid carcinoma. High index of suspicion in patients with TMG with other risk factors for malignancy requires careful evaluation to detect cancer.

Human ; Female ; Aged ; Goiter ; Immunoglobulins, Thyroid-stimulating ; Receptors, Thyrotropin ; Thyroid Carcinoma, Anaplastic ; Thyroid Hormones ; Thyroid Neoplasms ; Thyroid Nodule ; Thyroidectomy ; Hyperthyroidism

INTRODUCTION: Current guidelines recommend that in patients presenting with clinically palpable nodules or with an ultrasound finding of a thyroid nodule, one has to evaluate its risk for malignancy by proceeding with a fine needle aspiration biopsy (FNAB). The decision to do FNAB would depend on ultrasonographic features of the nodule, which include its size, hypoechogenicity, presence of microcalcifications, increased central vascularity, infiltrative margins, and taller than wide measures on transverse plane. Elastography, a measure of tissue stiffness, is now also being utilized as another feature that has a positive correlation with malignancy. This study hopes to determine which among the abovementioned ultrasonographic features would best correlate with a higher risk for thyroid malignancy among adult patients who had undergone ultrasound guided FNAB.
METHODOLOGY: A prospective study was done in a cohort of all Filipino patients 19 years old and above who underwent ultrasound guided FNAB of the thyroid nodule/s from July to December 2013 at the Radiology Section of The Medical City, Pasig City, Philippines. Specimen obtained from FNAB were then reviewed by a pathologist to determine its cytopathology and categorized based on the Bethesda System of Classification. The cytopathology reports were correlated with the features seen on the patient's thyroid ultrasound to determine which characteristic would be predictive of malignancy.
RESULTS: A total of 100 patients underwent ultrasoundguided FNAB, from which 157 nodules were biopsied. 27 nodules were excluded from the analysis due to non-diagnostic or unsatisfactory (Bethesda Category I) findings on cytopathology. Among the 100 patients, 86% of which were females with the mean age of 41 ± 11.31 in those found to have malignant cytopathologic diagnosis. Of the 130 nodules biopsied, 115 nodules were identified as benign (Bethesda Category II) while 15 were identified to be malignant or suspicious for malignancy (Bethesda Category III-VI). Each of the five sonographic features that were predictive of malignancy was compared between the two outcome groups (benignversus malignant). Among them, only the presence of microcalcifications on ultrasound showed to be significantly correlated with malignancy with an odds ratio of 11.3. Ultrasound evaluation with elastography was only performed on 24 nodules and hence results were inconclusive. A nodule possessing more than two of the ultrasound features that were predictive of malignancy was more likely to be malignant on cytopathology (p value of 0.00).
CONCLUSION: The presence of microcalcifications on thyroid nodules as seen on ultrasound is a significant predictor of malignancy and remains to be consistent locally as with foreign studies. Nodules that were proven to be malignant on cytopathology presented with more of the ultrasound features that are said to be predictive of malignancy.

Human ; Male ; Female ; Middle Aged ; Adult ; Thyroid Nodule ; Biopsy, Fine-needle ; Elasticity Imaging Techniques ; Thyroid Neoplasms ; Ultrasonography ; High-energy Shock Waves ; Calcinosis

Background: Guidelines for testing human epidermal growth factor receptor 2 (HER2) in breast cancer using fluorescence in situ hybridization (FISH) were released in 2018. These guidelines were jointly developed by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) to achieve a clearer designation of breast cancer HER2 status. Clinical correlation with other factors was also considered appropriate, especially for those cases classified under ISH groups 2, 3, and 4. Objective: In this study, we examined clinicopathologic features among Filipino breast cancer patients whose HER2 status was reclassified based on the 2018 ASCO/CAP guidelines. Methodology: One hundred and thirty-two (132) breast cancer cases with immunohistochemistry (IHC) equivocal results in the Medical City were enrolled from January 2017 up to December 2020. HER2 FISH results classified under groups 2, 3, and 4 were then re-evaluated for HER2-IHC status in accordance with the 2018 ASCO/CAP guidelines. The relationship between clinicopathologic features and HER2 status was analyzed using the Fisher exact test. Results: Significant differences were found in histologic type, nuclear pleomorphism, mitotic rate, progesterone receptor (PR) status, and regional lymph node involvement among the reclassified ISH groups. In the conv+ group, the tumor cells did not involve the regional lymph nodes as compared to group 5, where the tumor cells were involved. The conv- group had a higher grade for nuclear pleomorphism, mitotic count, and overall Nottingham Histologic Grade than group 5. There was a significant association between progesterone receptors among the conv- group and group 1. Conclusion Filipino breast cancer cases whose HER2 status was reclassified to negative following the 2018 ASCO/CAP guidelines had statistically different clinicopathologic features from those classified as group 5.
Breast Neoplasms ; Immunohistochemistry

Background: Fine-needle aspiration biopsy (FNAB) is the most accurate and cost-effective method to evaluate thyroid nodule for possible malignancy. However, an adequate specimen is required for proper examination by a pathologist. Rapid on-site evaluation (ROSE), a service typically provided by pathologists, is the real-time evaluation for adequacy of FNAB smears which can help improve adequacy rates by allowing the submission of additional thyroid samples when the submitted samples are inadequate. This study aims to investigate if ROSE done by trained Endocrinologists can improve specimen adequacy in our patients. Methods: A total of 192 patients were included in this study and were divided in two groups: a ROSE group (n=96) and a non-ROSE group (n=96). In the ROSE group, the smear of thyroid aspirate was evaluated for adequacy by a trained Endocrinologist in real time. In the non-ROSE group, specimens are directly sent to the Pathologist. Results: ROSE done by Endocrinologists had 94% sensitivity, 46% specificity and 82% accuracy compared to a Pathologist. The adequacy rate under the ROSE group was 84.38% and 81.25% in non-ROSE group. Conclusion Our study showed that ROSE can improve adequacy rate in our center. ROSE can also be used by physicians in the provinces who are performing FNAB of the thyroid without ultrasound guidance to improve specimen adequacy and lessen repeat biopsy.
Rapid On-site Evaluation

Background: A fine needle aspiration biopsy has been established as a safe, minimally invasive procedure in evaluation of salivary gland lesions. The complex overlapping cytomorphology of these lesions are challenging for pathologists, hence the introduction of an evidence-based system, the Milan System of Reporting Salivary Gland Cytopathology, to improve overall patient care. The study was taken up to reclassify salivary gland lesions from previous FNA biopsies in order to determine sensitivity, specificity, positive and negative predictive values of FNA, and evaluate the risk of malignancy of the various categories of the Milan system. Methodology: This was a 6-year retrospective descriptive study in a tertiary medical center. All salivary gland FNA cases were reviewed by two pathologists, and re-classified into the six categories of the Milan System. The number of false positive, false negative, true positive and true negative cases were obtained by comparing with the final histopathology diagnosis, and the risk of malignancy per category were calculated. Results: A total of 76 cases were reviewed and the overall average of the two readers diagnostic accuracy were 85.02% (95% CI: 84.50-85.60%), sensitivity and specificity were 80.77% (95% CI: 79.90-81.60%) and 86.19% (95% CI: 85.70-86.70%), respectively; positive and negative predictive values were 62.16% (95% CI: 60.70-63.60%) and 94.17% (95% CI: 94.00-94.40%), respectively. Conclusion The Milan System category with highest risk of malignancy was Malignant (Category VI – 100%). FNAB is still a reliable tool for clinicians, and use of the Milan System of Reporting Salivary Gland Cytopathology is beneficial in increasing efficacy of communication among clinicians to improve patient care.
Cytology ; Salivary Glands

Synchronous primary tumors of the urothelium and prostate are a diagnostic challenge among pathologists. Differentiating carcinomas of urothelial and prostatic origin requires careful assessment of histomorphology coupled with ancillary studies such as immunohistochemistry stains (IHC) to support the diagnosis. We report two cases of adult patients who underwent transurethral resection of the prostate (TURP), with two distinct morphologies noted on routine H&E sections. After a panel of immunohistochemical stains (HMWCK, CK5/6, CK7, CK20, GATA-3, p63, NKX3.1, and PSA), both cases were signed out as papillary urothelial carcinoma and prostatic acinar adenocarcinoma. Correlation of histomorphology with an IHC panel consisting of cytokeratins (CK5/6, CK7, CK20), a urothelial marker (GATA-3), and at least two prostatic markers (PSA, NKX3.1) is recommended in such cases.

Objectives: Known for their poor outcomes, triple negative breast cancers (TNBCs) have been investigated for immune checkpoint inhibitors that target Programmed death ligand 1 (PD-L1). In the recent decade, tumor-infiltrating lymphocytes (TILs) have also become potential biomarkers. The aim of the study is to determine the reproducibility of PD-L1 scoring system for TNBC (SP142 clone) and TILs interpretation in the local setting through intra- and interobserver agreement. Methodology: Forty-three primary resection specimens TNBC were evaluated on two occasions with PD-L1 (Roche VENTANA SP142 assay) and TILs by two breast pathologists and one general pathologist on physical glass slides. PD-L1 expression was determined by at least 1% positivity among immune cells within the tumoral area and contiguous peritumoral stroma while TILs was assessed based on International Immuno-Oncology Biomarker Working Group on Breast Cancer. Kappa statistic for PD-L1 and TILs categories while intraclass correlation coefficient (ICC) were assessed, with cutoffs of 0.80 and 0.70, respectively. Results: The overall interrater kappa statistic for PD-L1 on the first and second rounds were weak at 0.506 (95% CI: 0.334-0.679) and minimal at 0.314 (95% CI: 0.142-0.487), respectively. Intraobserver kappa statistic for PD-L1 were varied across the three readers while interobserver kappa values for PD-L1 showed none (0.181) to moderate (0.789) agreement. The TILs intraobserver reliability showed poor to good agreement, with the highest ICC of 0.889 (95% CI: 0.805-0.938). Conclusion This study demonstrated variable intra and interobserver agreement for both TILs and PD-L1 expression. Although it is desirable to have strong to almost perfect agreement, the kappa and ICC values suggest additional room for improvement. In light of the repercussions in management of patients who will undergo immune checkpoint inhibitor therapy, regular training sessions, concurrences of equivocal results, and possible use of digital pathology as a medium in interpreting TILs and PD-L1 stains to achieve consistent results.
Breast Neoplasms ; Triple Negative Breast Neoplasms ; Immunohistochemistry

This is a case of a 54-year-old, perimenopausal, Asian, woman, who presented with an enlarging left breast mass associated with whitish to bloody nipple discharge. A core needle biopsy, done in another institution, showed histologic findings of a mucinous carcinoma with triple negative “basal-like” biomarker status (ER, PR, HER2/neu). Six cycles of neoadjuvant chemotherapy were given after which the subsequent modified radical mastectomy revealed a centrally located, 10.0 cm, well-circumscribed, nodular, ovoid mass on gross examination. Microscopic findings showed tall columnar cells in stratification, tufts and papillary formations, with surrounding abundant extracellular mucin. The individual tumor cells exhibit enlarged, hyperchromatic, basally located nuclei with prominent nucleoli, abundant amphophilic and occasionally oncocytic cytoplasm which contains intracytoplasmic mucin. Based on the histologic features, “basal-like” biomarker expression, and additional immunohistochemical studies (positive CK7, negative CK20 and CDX2), this case demonstrates a pure mucinous cystadenocarcinoma of the breast. In addition to the rare histologic type, this case is exceptional since, despite multiple cycles of neoadjuvant chemotherapy, presence of extensive lymphovascular invasion and axillary lymph node involvement with extranodal extension remain evident.
Cystadenocarcinoma, Mucinous ; Breast Neoplasms