enhanced-communication-of-tumor-margins-using-3d-scanning-and-mapping

Enhanced Communication of Tumor Margins Using 3D Scanning and Mapping

After oncologic resection of malignant tumors, specimens are sent to pathology for processing to determine the surgical margin status. These results are ...

Vanderbilt University Medical Center

The incidence of early onset oral tongue squamous cell carcinoma (OTC) has been increasing in the United States, and no clear etiology has been identified. Studies on this topic have generally been small and presented varied results. The goal of this review is to analyze and synthesize the literature regarding early onset OTC risk factors, outcomes, and molecular analyses within the US. To date, studies suggest that early onset OTC patients tend to have less heavy cigarette use than typical onset patients, but there may be an association between early onset OTC and smokeless tobacco (chewing tobacco and snuff) use. Early onset OTC is associated with similar or possibly improved survival compared to typical onset OTC. There has been no evidence to support a significant role for human papillomavirus in development of early onset OTC. Further research with larger cohorts of these patients is needed to better characterize this disease entity.

Early onset oral tongue cancer in the United States: A literature review.

After being described in the salivary glands as a malignancy with features essentially identical to those of the breast, secretory carcinoma (SC) (formerly mammary analogue SC) has now been identified in other sites including the skin, lung, and thyroid gland. In the breast, SC has a relatively favorable prognosis. Likewise when arising in the salivary glands, it is generally considered to be a low to intermediate grade carcinoma; however, there is a range of clinical behavior with occasional patients dying of progressive disease. SCs of the thyroid gland are rare, and reports suggest a relatively aggressive behavior, at least relative to well differentiated carcinomas such as papillary carcinoma and minimally invasive follicular carcinoma. We present a patient with a highly aggressive thyroid gland SC that mimicked undifferentiated carcinoma clinically. The patient had widespread metastatic disease and died rapidly from airway compromise. We also review the literature for reported cases of thyroid gland SC in order to better establish the clinical features and expected clinical course of such tumors occurring at this site.

Secretory Carcinoma of the Thyroid Gland: Report of a Highly Aggressive Case Clinically Mimicking Undifferentiated Carcinoma and Review of the Literature.

Human papillomavirus (HPV) has become a critical prognostic biomarker in oropharyngeal squamous cell carcinoma (OPSCC). While retrospective studies suggest that p16 immunohistochemistry and even HPV RNA in situ hybridization work well on tissues and tumors from a variety of labs and various fixation conditions, no formal study of fixation conditions has been performed to date. We took surgically resected specimens from three p16 and HPV RNA in situ hybridization positive OPSCC patients, divided their fresh tumors into small pieces, and varied the time to formalin fixation as 1, 3, 6, 24, and 48 h. Tumors were either held moistened at room temperature or were refrigerated. After fixation and processing, routine hematoxylin and eosin slides were generated and p16 immunohistochemistry and RNA in situ hybridization performed. All three tumors were nonkeratinizing and had strong and diffuse p16 expression at immediate fixation, which, surprisingly, remained positive for all fixation times and conditions and despite significant degeneration at the later points for two of the patients while for one, the nuclear signal dropped out of most cells at early and mid time points, particularly at room temperature, causing false negatives. HPV RNA in situ hybridization stayed positive in all specimens up to 48 h of cold ischemic time refrigerated and even at room temperature, except for overtly autolyzed tumor regions. These findings help to establish that, at least for standard nonkeratinizing, p16 and HPV RNA strongly positive OPSCC patients, and using the most common tests in clinical practice, relatively lenient time to fixation may be acceptable if it cannot be avoided. However, for some patients, p16 immunohistochemistry may be sensitive to signal loss with autolysis. HPV RNA in situ hybridization, in particular, seems remarkably resistant to pretest cold ischemic times.

Tissue Fixation Conditions for p16 Immunohistochemistry and Human Papillomavirus RNA In Situ Hybridization in Oropharyngeal Squamous Cell Carcinoma.

High risk human papillomavirus (HPV) has transformed head and neck oncology in the past several decades. Now that we have recognized that HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) is a unique cancer type with distinct clinicopathologic features and favorable prognosis, it has become essential to test patients in routine practice. We have progressed greatly in our knowledge of this disease and gone, over the past two to three decades, from doing testing in highly variable amounts and methods to, now, with the help of national and international guidelines and patient staging requirements, to a situation where almost all patients with OPSCC are getting accurate classification through at least p16 immunohistochemistry. However, we are still struggling with how to accurately test specimens from cervical lymph nodes, and, in particular, on fine needle aspiration. In addition, many patients with non-oropharyngeal SCC are getting clinically unnecessary p16 and/or HPV-specific testing. The trends suggest progressive improvement in practices, but many practical questions still remain. On the horizon are myriad non-tissue-based tests, such as HPV serology and plasma DNA, DNA-based testing of fine needle aspirate fluid, computerized analysis of digitized pathology and radiology images, and machine learning from clinical and pathologic features, that may render pathologists largely obsolete for establishing HPV status for our patients' tumors. This review takes a brief look back in time to where we have been, then characterizes current practices in 2020 and lingering questions, and, finally, looks ahead into the possible future of HPV testing in patients with head and neck SCC.

Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma in 2020: Where Are We Now and Where Are We Going?

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.

Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages.

There have been a few case reports and one small series of low grade papillary sinonasal (Schneiderian) carcinomas (LGPSC) which mimic papillomas but have overtly invasive growth and which occasionally metastasize. We describe the morphologic, clinical, immunohistochemical, and molecular features of five patients with LGPSC compared with eight cases each of inverted papilloma (IP) and conventional nonkeratinizing squamous cell carcinoma (SCC) with papillary growth. All LGPSC were nested with predominantly pushing invasion, no stromal reaction, and frequent surface papillary growth. All consisted of one cell type only, with polygonal cells with round nuclei, no (or limited) cytologic atypia, low mitotic activity, and prominent neutrophilic infiltrate. One patient had slightly more infiltrative bone invasion, another lymphovascular, perineural, and skeletal muscle invasion, and a third nodal metastasis after 17 years. By comparison, IPs had bland cytology, neutrophilic microabscesses, mixed immature squamous, goblet cell, and respiratory epithelium, and extremely low mitotic activity. Nonkeratinizing SCCs had basaloid-appearing cells with nuclear pleomorphism, brisk mitotic activity, and apoptosis. All LGPSC were p63 positive. Mitotic activity and Ki67 indices were significantly higher for LGPSCs than IPs and significantly lower than NKSCCs, while p53 immunohistochemistry in LGPSC was identical to nonkeratinizing SCC and higher than for IP. Sequencing showed all five tumors to harbor a MUC6 mutation, one tumor to harbor CDKN2A and PIK3R1 mutations, and one tumor to harbor a NOTCH1 mutation. All LGPSC lacked EGFR and KRAS mutations and lacked copy number variations of any main cancer genes. At a median follow up of 12 months, two LGPSC recurred locally, and one patient died after massive local recurrences and nodal metastases. LGPSC is a distinct, de novo sinonasal carcinoma that can be differentiated from papillomas by morphology and selected immunohistochemistry.

Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous Cell Carcinoma.

Tissue slides from Oral cavity squamous cell carcinoma (OC-SCC), particularly the epithelial regions, hold morphologic features that are both diagnostic and prognostic. Yet, previously developed approaches for automated epithelium segmentation in OC-SCC have not been independently tested in a multi-center setting. In this study, we aimed to investigate the effectiveness and applicability of a convolutional neural network (CNN) model to perform epithelial segmentation using digitized H&E-stained diagnostic slides from OC-SCC patients in a multi-center setting.

A machine learning model for separating epithelial and stromal regions in oral cavity squamous cell carcinomas using H&E-stained histology images: A multi-center, retrospective study.

HPV-associated oral cavity squamous cell carcinoma (SCC) is not well-characterized in the literature, and also has a clinical significance that is poorly understood.

Human Papillomavirus-Associated Oral Cavity Squamous Cell Carcinoma: An Entity with Distinct Morphologic and Clinical Features.

Sinonasal adenosquamous carcinoma is rare, and there are almost no studies detailing morphology or characterizing their genetic driver events. Further, many authors have termed sinonasal tumors with combined squamous carcinoma and glands as mucoepidermoid carcinoma but none have analyzed for the presence of MAML2 rearrangement.

Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement.

Article	Year
Early onset oral tongue cancer in the United States: A literature review. Oral oncology\| PubMed ID: 30527223	2018
Secretory Carcinoma of the Thyroid Gland: Report of a Highly Aggressive Case Clinically Mimicking Undifferentiated Carcinoma and Review of the Literature. Head and neck pathology\| PubMed ID: 30564997	2019
Tissue Fixation Conditions for p16 Immunohistochemistry and Human Papillomavirus RNA In Situ Hybridization in Oropharyngeal Squamous Cell Carcinoma. Head and neck pathology\| PubMed ID: 31628584	2020
Human Papillomavirus Testing in Head and Neck Squamous Cell Carcinoma in 2020: Where Are We Now and Where Are We Going? Head and neck pathology\| PubMed ID: 32124415	2020
Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages. Head and neck pathology\| PubMed ID: 33797697	2021
Low Grade Papillary Sinonasal (Schneiderian) Carcinoma: A Series of Five Cases of a Unique Malignant Neoplasm with Comparison to Inverted Papilloma and Conventional Nonkeratinizing Squamous ... Head and neck pathology\| PubMed ID: 34041710	2021
A machine learning model for separating epithelial and stromal regions in oral cavity squamous cell carcinomas using H&E-stained histology images: A multi-center, retrospective study. Oral oncology\| PubMed ID: 35689952	2022
Human Papillomavirus-Associated Oral Cavity Squamous Cell Carcinoma: An Entity with Distinct Morphologic and Clinical Features. Head and neck pathology\| PubMed ID: 35802245	2022
Sinonasal Adenosquamous Carcinoma - Morphology and Genetic Drivers Including Low- and High-Risk Human Papillomavirus mRNA, DEK::AFF2 Fusion, and MAML2 Rearrangement. Head and neck pathology\| PubMed ID: 36849671	2023

Jim Lewis

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