Computerized tumor multinucleation index (MuNI) is prognostic in p16+ oropharyngeal carcinoma.

BACKGROUNDPatients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure for p16+ OPSCC. Pathologist-based visual assessment of tumor cell multinucleation (MN) has been shown to be independently prognostic of disease-free survival (DFS) in p16+ OPSCC. However, its quantification is time intensive, subjective, and at risk of interobserver variability.METHODSWe present a deep-learning-based metric, the multinucleation index (MuNI), for prognostication in p16+ OPSCC. This approach quantifies tumor MN from digitally scanned H&E-stained slides. Representative H&E-stained whole-slide images from 1094 patients with previously untreated p16+ OPSCC were acquired from 6 institutions for optimization and validation of the MuNI.RESULTSThe MuNI was prognostic for DFS, overall survival (OS), or distant metastasis-free survival (DMFS) in p16+ OPSCC, with HRs of 1.78 (95% CI: 1.37-2.30), 1.94 (1.44-2.60), and 1.88 (1.43-2.47), respectively, independent of age, smoking status, treatment type, or tumor and lymph node (T/N) categories in multivariable analyses. The MuNI was also prognostic for DFS, OS, and DMFS in patients with stage I and stage III OPSCC, separately.CONCLUSIONMuNI holds promise as a low-cost, tissue-nondestructive, H&E stain-based digital biomarker test for counseling, treatment, and surveillance of patients with p16+ OPSCC. These data support further confirmation of the MuNI in prospective trials.FUNDINGNational Cancer Institute (NCI), NIH; National Institute for Biomedical Imaging and Bioengineering, NIH; National Center for Research Resources, NIH; VA Merit Review Award from the US Department of VA Biomedical Laboratory Research and Development Service; US Department of Defense (DOD) Breast Cancer Research Program Breakthrough Level 1 Award; DOD Prostate Cancer Idea Development Award; DOD Lung Cancer Investigator-Initiated Translational Research Award; DOD Peer-Reviewed Cancer Research Program; Ohio Third Frontier Technology Validation Fund; Wallace H. Coulter Foundation Program in the Department of Biomedical Engineering; Clinical and Translational Science Award (CTSA) program, Case Western Reserve University; NCI Cancer Center Support Grant, NIH; Career Development Award from the US Department of VA Clinical Sciences Research and Development Program; Dan L. Duncan Comprehensive Cancer Center Support Grant, NIH; and Computational Genomic Epidemiology of Cancer Program, Case Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, the US Department of VA, the DOD, or the US Government.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a review for pathologists.

The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing 'Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).' This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.

Small round blue cell tumors of the sinonasal tract: a differential diagnosis approach.

One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached. Discrimination between neoplasms is critical as there are significant differences in therapy and overall outcome. It is important to have a well developed differential diagnosis for this category of tumors, where each of the diagnoses is considered, evaluated, and either confirmed or excluded from further consideration. In an undifferentiated tumor, showing a small round blue cell morphology, using the mnemonic 'MR SLEEP' helps to highlight tumors to consider: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), Ewing sarcoma/primitive neuroectodermal tumor, pituitary adenoma, and plasmacytoma. A panel of pertinent immunohistochemistry studies, histochemistries and/or molecular tests should aid in reaching a diagnosis, especially when taking the pattern and intensity of reactions into consideration.

Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment.

Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or >3 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3 mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).