Tall cell variant papillary thyroid carcinoma impacts disease-free survival at the 10 % cut-point on multivariate analysis.

INTRODUCTION: The diagnosis of tall cell variant papillary thyroid carcinoma (TCV-PTC) corresponds to the feature of "aggressive histology" within the framework of the American Thyroid Association (ATA) Risk of Recurrence (ROR) guidelines. Using the current World Health Organization (WHO) definition for TCV-PTC (tall cells with height at least twice the width, distribution ≥ 30 %), we examined the impact of this diagnosis on disease-free survival (DFS). METHODS: The study cohort consisted of 347 patients treated for primary papillary thyroid carcinoma (PTC). Current ATA guidelines were followed for the extent of surgery and the administration of adjuvant radioiodine therapy. Clinical surveillance included ultrasound examination and biochemical parameters according to ATA standards. The outcome was measured as time from surgery to first disease recurrence (DR) versus time from surgery until the last documented disease-free encounter (no evidence of disease, NED). Disease-free patients with fewer than 6 months of follow-up were excluded from this cohort. Structural recurrences are documented by histology or cytology whereas biochemical recurrences are documented by rising serum thyroglobulin in the absence of structural disease. All slides on all patients were examined by two pathologists with the substantial interobserver agreement (Kappa = 73 %). The primary tumors are categorically classified either as (1) TCV-PTC (definition above), (2) Papillary thyroid carcinoma with tall cell features (PTC-TCF) (≥ 10 % < 30 % tall cells), or (3) Control (< 10 % tall cells). Tumor size is categorized as either (1) ≤ 10 mm, (2) 11-29 mm, or (3) ≥ 30 mm. Degree of ETE is categorized as either intrathyroidal, microscopic ETE, histologic spread to strap muscles, or pT4 disease. RESULTS: 185 patients are classified as TCV-PTC (≥ 30 % tall cells), 62 as PTC-TCF (≥ 10 % < 30 % tall cells), and 100 as control group (< 10 % tall cells). TCV-PTC is associated with ≥ 30 mm size (p = .0246) and invasion of strap muscles and/or pT4 (p = .0325). There was no relationship between TCV-PTC and aggressive lymph node (ALN) status defined by ATA. Overall follow-up ranged from two months (one patient death) to 203 months (mean 40.8, median 33.0). DR occurred in 61 patients (mean 31.4 months, range 0 -184, 59 structural recurrences, 2 biochemical recurrences). Three models for TCV-PTC were examined: Model 1 - Tall cells ≥ 10% versus control, Model 2 - TCV-PTC versus TCF-PTC versus control, and Model 3 - TCV-PTC versus control. Kaplan Meier curves demonstrated decreased DFS with ALN status (p = .0001), ETE (p = .0295), and TCV-PTC (Model 1, p = .041). On multivariate analysis, TCV-PTC (Model 1) remained significantly predictive when adjusted for ALN (p = .0059). ETE dropped out of the model. CONCLUSION: TCV-PTC is significantly associated with larger tumors and a greater degree of ETE. The diagnosis of TCV-PTC significantly impacts DFS at the 10 % cut-point on multivariate analysis.

BIA-ALCL diagnosis on CytoLyt fixed ThinPrep, cell block and immunohistochemistry.

Breast implant associated anaplastic large cell lymphoma (BIA-ALCL) is an emergent rare T cell non-Hodgkin lymphoma arising in association with a breast implant, particularly textured ones. Recent guidelines list cytopathological examination as the first essential step for diagnosis, routinely followed by CD30 immunohistochemistry (IHC) and flow cytometry (FC) for a T cell clone. The majority of BIA-ALCL literature regarding cytopathological evaluation describes morphology based on various preparation methods limited to cytospins and smears with the exception of at least one case report detailing cytomorphological and IHC findings on ThinPrep. This case report details initial diagnosis of BIA-ALCL rendered with CytoLyt prepared ThinPrep and cell block, including the specific antibodies used for IHC. The ThinPrep slide showed numerous singly dispersed large, atypical cells with abundant cytoplasm containing irregular nuclei with dispersed chromatin and prominent nucleoli in a background of macrophages, inflammatory cells and granular debris. TIA-1 and CD30 along with other T-cell markers, including specific antibodies, remains immunoreactive in tissue collected in CytoLyt solution. Cell size reduction, artifactual lymphoid cell aggregation and prominent nucleoli in benign and reactive conditions are among other ThinPrep cellular alterations pathologists should bear in mind.

The significance of ASC-H and LSIL dual interpretation with risk stratification: one institution experience.

INTRODUCTION: The 2014 Bethesda System categorizes squamous lesions as low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL). It also includes intermediate morphologic terminology, such as atypical squamous cells of undetermined significance (ASC-US) and atypical squamous cells, cannot rule out a high grade squamous intraepithelial lesion (ASC-H). Consensus is lacking if when ASC-H is present in an unequivocal LSIL (LSIL + ASC-H) versus ASC-H alone predicts a neoplasm with a different biologic behavior and which is its association with high-risk human papillomavirus (HPV). MATERIALS AND METHODS: We reviewed the Columbia University Medical Center Pathology department patient's database from October 2012 through December 2014 and found 2498 cytology samples of LSIL, ASC-H, HSIL, and LSIL + ASC-H with both follow-up histologic samples and HPV tests by Roche cobas. Our objective was to identify, if any, differences in biologic behavior and HPV status present in LSIL + ASC-H compared with ASC-H and other lesions. RESULTS: CIN2+ was documented in tissue examination in 102 from 311 LSIL + ASC-H (32.8%), 101 from 219 ASC-H (46.1%), 252 from 326 HSIL+ (77.3%), and 150 from 1642 LSIL (9.08%). HPV distribution shows significant differences between all diagnostic categories. CONCLUSIONS: LSIL + ASC-H appears to have a distinctive HPV distribution pattern that clearly differs from ASC-H and LSIL and approaches HSIL; however, the predictive value for CIN2+ appears higher for ASC-H than LSIL + ASC-H. Our literature review identified conflicting findings, probably suggesting a lack of reproducibility in cytologic criteria and the need for consistent inclusion of ASC-H and LSIL when both are present.

Oral squamous carcinoma: Aggressive tumor pattern of invasion predicts direct mandible invasion.

BACKGROUND: Aggressive histologic worst pattern of invasion (WPOI) in surrounding soft tissue has been shown to be predictive of higher local recurrence and poorer survival in oral cavity squamous cell carcinoma (OCSCC) patients. This study investigates whether aggressive WPOI can predict the mandibular invasion phenotype. METHODS: Patients consecutively diagnosed with OCSCC undergoing a mandibulectomy (marginal or segmental) between 2013 and 2018 were reviewed. Senior physicians re-reviewed radiologic scans and pathologic slides of 44 cases. RESULTS: Aggressive WPOI (WPOI-4, 5) is significantly associated with infiltrative bone invasion. Non-aggressive WPOI (WPOI-1, 2, 3) is significantly associated with the absence of bone invasion. CONCLUSIONS: WPOI has become a useful tool that further characterizes the biologic behavior of OCSCC. Potentially, planned surgery may escalate from a marginal to segmental mandibulectomy based on aggressive WPOI for patients with radiographically uncertain cortical status. Further studies are needed to validate the relationship between OCSCC WPOI and mandible status.

Ten patients with high-grade transformation of acinic cell carcinomas: Expression profiling of ß-catenin and cyclin D1 is useful.

Conventional acinic cell carcinoma (CACC) represents a prototypical low-grade salivary malignancy. Rarely, acinic cell carcinoma (ACC) can demonstrate aggressive features (zones of necrosis, apoptosis, varying nuclear atypia) warranting classification as "ACC with high-grade transformation" (HGT-ACC) or "dedifferentiated" ACC. This study reports ten new cases of HGT-ACC. There is potential for subtlety in recognizing high-grade transformation and distinguishing discrete nodules of necrosis from cytology aspiration changes. We compared immunohistochemical (IHC) profiles, specifically ß-catenin (bCAT) and cyclin D1 expression, which have been touted as potentially helpful in this context. We quantified morphology (primary axis nucleus, nuclear area and perimeter) in HGT-ACC and CACC. Clinical outcome is known for eight HGT-ACC patients; three patients developed locoregional or distant metastases, five remained disease-free. Nine of ten HGT-ACC expressed strong, diffuse, membranous bCAT. CACC demonstrated lower intensity of membranous bCAT expression. Strong, diffuse nuclear cyclin D1 was seen in five of ten HGT-ACC whereas no CACC demonstrated cyclin D1 with distribution greater than 50 %. The quantified nuclear morphologic features of CACC and HGT-ACC demonstrated overlapping means values. Maximum values for nuclear primary axis, area, and perimeter were greater for HGT-ACC versus CACC, corresponding to a subpopulation of larger tumor cells in HGT-ACC. The poor outcome associated with HGT-ACC justifies its recognition, which should alter surgical approach with respect to elective neck dissection or possible facial nerve sacrifice. With respect to ancillary IHC studies, strong, diffuse membranous bCAT expression, with or without strong nuclear cyclin D1 ≥ 50 % distribution or Ki67 index ≥ 25 % supports this diagnosis.

The role of molecular testing in the diagnosis of medullary thyroid cancer: A case report of oncocytic medullary thyroid carcinoma and review of the literature.

BACKGROUND: Medullary thyroid carcinoma (MTC) is a somewhat rare, particularly aggressive form of thyroid cancer. The authors present what we believe to be the first case of MTC diagnosed solely on the basis of molecular testing, as well as a review of the literature concerning this topic and oncocytic variants of MTC. CASE DESCRIPTION: A 30-year-old female patient with a 1.1 cm thyroid nodule underwent a fine-needle aspiration biopsy showing a Bethesda IV Hurthle cell neoplasm. Molecular testing of the specimen identified a RET M918 T mutation. The patient underwent a total thyroidectomy and bilateral central neck dissection. Initial pathologic analysis yielded a diagnosis of Hurthle cell adenoma. Based on the patient's known RET mutation, immunohistochemistry for calcitonin was performed and yielded a positive result. The final diagnosis was amended to an oncocytic variant of medullary thyroid carcinoma. DISCUSSION: Had this patient undergone fine-needle aspiration (FNA) biopsy without molecular testing or serum calcitonin measurement, the patient's disease would have been diagnosed as a Hurthle cell adenoma. Despite the lack of characteristic features of malignancy and the rarity of oncocytic MTC, the diagnostic pitfall in this oncocytic lesion was avoided due to molecular testing at the time of FNA biopsy. CONCLUSION: This case draws attention to the unique clinical value of molecular testing in the diagnosis of MTC. The authors believe this case supports the consideration for molecular testing to prevent missed diagnoses in cases of rare benign-appearing disease.

Primary breast cancer of the vulva with concurrent breast and endometrial cancers: A case report and literature review.

•Breast cancer originating from the vulva is extremely rare.•There are no guidelines for the treatment of such cancers.•More research is needed to uncover a possible genetic predisposition.