Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: An interobserver study of key cytomorphological features from a large academic medical centre.

OBJECTIVE: Because of the indolent nature of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and potential requisite for a more conservative treatment, it is crucial to identify features of this entity preoperatively. Our group recently published findings that there are several cytomorphological features that may be used as clues to distinguish NIFTP, papillary thyroid carcinoma (PTC) and follicular adenoma (FA) on fine needle aspiration. Therefore, we aimed to determine the interobserver reproducibility of these findings. METHODS: Presurgical fine-needle aspiration slides from NIFTP (n = 30), classic PTC (n = 30) and FA (n = 30) collected from 1/2013-8/2016 were reviewed by seven cytopathologists blindly. Presence of selected cytomorphological 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 cytomorphological features, the overall percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's AC1 0.30-0.80). There was substantial or almost perfect agreement (Gwet's AC1 > 0.60) in seven cytomorphological 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 cytological profile, these cytomorphological features may assist the cytopathologist in raising the possibility of NIFTP preoperatively. This can potentially aid clinicians in deciding whether more conservative treatment may be appropriate.

Bronchiolar Adenoma/Pulmonary Ciliated Muconodular Papillary Tumor.

OBJECTIVES: To describe the histologic features that are helpful in the diagnosis of the rare bronchiolar adenomas/ciliated muconodular papillary tumors (BAs/CMPTs) during intraoperative consultation. METHODS: Multi-institutional retrospective review of frozen sections of 18 BAs/CMPTs. RESULTS: In 14 of 18 cases, BA/CMPT was the primary reason for sublobar lung resection, and in 4 cases, BA/CMPT was an incidental finding intraoperatively for resections performed for carcinoma in other lobes. There were 11 proximal-type/classic BAs/CMPTs and 7 distal-type/nonclassic BAs/CMPTs. Only 3 (16.7%) of 18 were correctly diagnosed at the time of frozen section, all of which were proximal type/classic. The remainder were diagnosed as adenocarcinoma (n = 7); invasive mucinous adenocarcinoma (n = 1); non-small cell lung carcinoma (n = 1); cystic mucinous neoplasm, favor adenocarcinoma (either mucinous or colloid type) (n = 1); favor adenocarcinoma, cannot exclude CMPT (n = 1); atypical proliferation (n = 2); mucinous epithelial proliferation (n = 1); and mucous gland adenoma (n = 1). CONCLUSIONS: BA/CMPT can potentially be misdiagnosed as carcinoma during intraoperative consultation. On retrospective review of the frozen sections, the presence of the following may help to avoid misdiagnosis: a mixture of bland ciliated columnar cells, mucinous cells, and, most important, a basal cell layer, as well as a lack of necrosis, significant atypia, and mitoses.

Scoring of Programmed Death-Ligand 1 Immunohistochemistry on Cytology Cell Block Specimens in Non-Small Cell Lung Carcinoma.

OBJECTIVES: Recent investigations have shown strong correlations between cytology and surgical non-small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement. METHODS: PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (<1%), low positive (1%-49%), and high positive (≥50%) and interrater agreement were assessed. RESULTS: Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with κ = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (κ = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (κ = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters. CONCLUSIONS: There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.

Adult rhabdomyoma presenting as thyroid nodule on fine-needle aspiration in patient with Birt-Hogg-Dubé syndrome: Case report and literature review.

Extracardiac rhabdomyoma is an uncommon benign striated muscle tumor with a predilection for the head and neck region. However, it is extremely rare for extracardiac rhabdomyoma to present as a thyroid nodule. We report a case of rhabdomyoma diagnosed by thyroid fine-needle aspiration (FNA) in a patient with Birt-Hogg-Dubé (BHD) syndrome. A 60-year-old man with BHD syndrome presented for recurrent pneumothorax. Chest CT incidentally identified a thyroid nodule. Subsequent sonography confirmed a 4.44 × 2.28 × 2.82 cm solid, hypoechoic nodule with smooth margins in the right upper pole. Ultrasound-guided FNA revealed many clusters and scattered isolated large polygonal cells with abundant granular cytoplasm and small peripherally located nuclei. Vague striations in the cytoplasm were focally identified. No follicular cells or colloid was present. Immunocytochemistry on one direct smear slide demonstrated diffuse positivity for desmin, supporting muscular differentiation. Subsequent surgery identified an adult rhabdomyoma originating from the inferior constrictor muscle of the neck and anteriorly displacing the thyroid. Because the mass was intimately associated with the thyroid gland, it was initially mistaken for a thyroid nodule on ultrasound. Diagnosis of rhabdomyoma on FNA is challenging, especially when rhabdomyoma mimics a thyroid nodule on imaging. The differential diagnosis includes Hurthle cell neoplasm, granular cell tumor, colloid nodule, and normal striated skeletal muscle. Adequate radiologic data and familiarity with the cytologic features of rhabdomyoma are critical for an accurate diagnosis.

Sarcomatoid carcinoma in cytology: Report of a rare entity presenting in pleural and pericardial fluid preparations.

Sarcomatoid carcinoma is rarely found in pleural or pericardial fluid, with very few cases published to date. Here, we describe a 59-year-old female who presented with cough persisting for 5 months. Chest CT scan revealed a 6.0 cm cavitary mass in the left lung base with bulky mediastinal and hilar lymphadenopathy. An additional 1.2 cm right adrenal mass was seen and was suspicious for metastatic disease. The patient developed dyspnea, tachycardia, pleuritic chest pain and generalized weakness and was admitted to the hospital. She was found to have pleural and pericardial effusions, which were drained and sent to cytology. The fluid revealed enlarged highly pleomorphic malignant cells, some displaying multinucleation with irregular nuclear borders, coarse chromatin and prominent nucleoli. Tumor cells were positive for CK7 and Vimentin and negative for MOC-31, Ber-EP4, B72.3, Sox10, Melan-A, TTF-1, Napsin-A and CK20. A concurrent surgical biopsy of the tumor mass displayed immunopositivity for AE1/AE3 and CAM5.2. The tumor was negative for p40, TTF-1, calretinin, D2-40 and STAT6. A diagnosis of sarcomatoid carcinoma with giant cells and spindle cells was rendered. Sarcomatoid carcinomas of the lung are very uncommon consisting of 1% of non-small-cell lung carcinomas and are even more unusual in cytology specimens. Despite its rarity, it is important to keep this entity in mind in the differential diagnosis of a fluid specimen with bizarre nuclear atypia and the above staining pattern.

Papillary thyroid carcinoma metastatic to the pancreas: Case report.

Papillary thyroid carcinoma (PTC) is generally associated with an excellent long-term outcome. Distant metastasis is rare with only 5-7% of patients developing distant disease. Metastasis of PTC to the pancreas is an exceedingly rare occurrence. To date, few cases have been reported. We present the case of an 81-year-old man with past medical history of PTC status post total thyroidectomy with local recurrence treated with radioactive iodine and selective neck dissection. Ten years after his initial diagnosis, PET-CT scan revealed a new hypermetabolic 1.1 cm × 0.9 cm left lower lobe lung nodule and hypermetabolism in the proximal body of the pancreas. Follow-up MRI cholangiogram showed a 1.0 × 0.8 cm T1 hypointense lesion in the proximal body of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration biopsy of the pancreatic mass showed neoplastic epithelial cells arranged in papillary clusters with fibrovascular cores and syncytial sheets with high nuclear to cytoplasmic ratio, visible nucleoli, nuclear pallor, focal nuclear grooves, and rare intranuclear pseudoinclusions. Immunohistochemical stains performed on the smears showed positive nuclear expression of TTF-1 and PAX-8. The findings were consistent with metastatic PTC. Surgical resection of the lung nodule confirmed metastatic PTC. Pancreatic metastases usually occur after long time intervals with reports of up to 8 years in PTC. This makes the diagnosis more challenging, and metastatic disease should always be in the differential diagnosis in cases presenting with a pancreatic mass, especially in patients with a prior malignancy.

TROP-2 expression in papillary thyroid carcinoma: Potential Diagnostic Utility.

TROP-2 is a type I transmembrane glycoprotein which is over-expressed in various malignancies, and is related to epithelial cell adhesion molecule (EpCAM), also called TROP-1, gp40, and KSA. In this study, we evaluated TROP-2 expression in papillary thyroid carcinoma (PTC) and compared it to other thyroid neoplastic and non-neoplastic lesions. Immunohistochemical (IHC) evaluation for TROP-2 was performed on 137 thyroid fine needle aspiration (FNA) cell blocks (CB) which included classic PTC (64), follicular variant PTC (FVPTC) (10), anaplastic thyroid carcinoma (AC) (2), medullary carcinoma (MC) (8), follicular neoplasms (FN) (8), Hurthle cell neoplasms (HCN) (9), follicular lesion of uncertain significance (FLUS) (12), and benign thyroid nodule (BTN) (24). IHC for TROP-2 expression was also performed on 331 BTN and malignant tumor tissue sections in tissue microarray (TMA). Membranous staining in >5% of tumor cells was considered positive. TROP-2 stained 61 of 64 PTC CB, 7 of 10 FVPTC CB, and 9 of 12 FLUS CB. All other cases were negative for TROP-2. TROP-2 showed a sensitivity of 95.31% and specificity of 89% for classic PTC in FNA CB. In TMA samples, TROP-2 stained 54 of 60 classic PTC cases and hence showed a high sensitivity and specificity. All BTN in CB and TMA were negative. We conclude that TROP-2 is a highly sensitive and specific IHC marker for identifying classic PTC. TROP-2 may play an important role in diagnosing classic PTC, especially in equivocal cases. This study also identifies a strong role for TROP-2 in separating PTC from BTN.

Metastatic balloon cell malignant melanoma: a case report and literature review.

A case of metastatic balloon cell malignant melanoma (BCMM) is presented. The balloon melanoma cells (BMC) were absent in the shave biopsy of the primary lesion and present as a minor component in the wide and deep excision. A subsequent right neck lymph node metastasis showed complete replacement of the lymph node by large, foamy cells. Though the tumor was amelanocytic and Fontana-Masson stain failed to reveal melanin, it stained positively for S-100, HMB-45, and Melan-A. Ultrastructurally, the foamy cells were characterized by cytoplasmic vacuolization and a lack of melanosomes. The differential diagnosis of metastatic balloon cell malignant melanoma is broad, and clinicopathologic correlation may play a critical role in achieving the correct diagnosis.