Category Archives: Oral Cavity/Gnathic (Jaw)

Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B, Prabhu AV, Lai C, Shuai Y, Carroll WR, Morlandt A, Duvvuri U, Kim S, Johnson JT, Ferris RL, Seethala R, Chiosea S.

JAMA Otolaryngol Head Neck Surg. 2015 Dec 1;141(12):1104-10.

IMPORTANCE: Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique.

OBJECTIVE: To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015.

INTERVENTIONS: In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR.

MAIN OUTCOMES AND MEASURES: Local recurrence.

RESULTS: Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin.

CONCLUSIONS AND RELEVANCE: The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

PubMed ID: 26225798

Article Size: <1 MB

 

Corredor G, Toro P, Koyuncu C, Lu C, Buzzy C, Bera K, Fu P, Mehrad M, Ely KA, Mokhtari M, Yang K, Chute D, Adelstein DJ, Thompson LDR, Bishop JA, Faraji F, Thorstad W, Castro P, Sandulache V, Koyfman SA, Lewis JS, Madabhushi A.

J Natl Cancer Inst. 2022 Apr 11;114(4):609-617. doi: 10.1093/jnci/djab215.

BACKGROUND: HPV-associated oropharyngeal squamous cell carcinoma (OPCSCC) has excellent control rates compared to non-virally associated OPSCC. Multiple trials are actively testing whether de-escalation of treatment intensity for these patients can maintain oncologic equipoise while reducing treatment related toxicity. We have developed OP-TIL, a biomarker that characterizes the spatial interplay between tumor-infiltrating lymphocytes (TILs) and surrounding cells in histology images. Herein, we sought to test whether OP-TIL can segregate stage I HPV-associated OPSCC patients into low-risk and high-risk groups and aid in patient selection for de-escalation clinical trials.

METHODS: Association between OP-TIL and patient outcome was explored on whole slide H&E images from 439 stage I HPV-associated OPSCC patients across six institutional cohorts. One institutional cohort (n = 94) was used to identify the most prognostic features and train a Cox regression model to predict risk of recurrence and death. Survival analysis was used to validate the algorithm as a biomarker of recurrence/death in the remaining five cohorts (n = 345). All statistical tests were 2-sided.

RESULTS: OP-TIL separated stage I HPV-associated OPSCC patients with ≤30 pack-year smoking history into low-risk (2-year disease-free survival [DFS] = 94.2%; 5-year DFS= 88.4%) and high-risk (2-year DFS = 82.5%; 5-year DFS = 74.2%) groups (hazard ratio = 2.56, 95% confidence interval = 1.52-4.32, P < .001), even after adjusting for age, smoking status, T and N-classification, and treatment modality on multivariate analysis for DFS (hazard ratio = 2.27, 95% confidence interval = 1.32-3.94, P = .003).

CONCLUSIONS: OP-TIL can identify stage I HPV-associated OPSCC patients likely to be poor candidates for treatment de-escalation. Following validation on previously completed multi-institutional clinical trials, OP-TIL has the potential to be a biomarker, beyond clinical stage and HPV status, that can be used clinically to optimize patient selection for de-escalation.

PubMed ID: 34850048

Article Size: 1.9 MB

Thompson LDR, Fitzpatrick SG, Müller S, Eisenberg E, Upadhyaya JD, Lingen MW, Vigneswaran N, Woo SB, Bhattacharyya I, Bilodeau EA, Carlos R, Islam MN, Leon ME, Lewis JS Jr, Magliocca KR, Mani H, Mehrad M, Purgina B, Richardson M, Wenig BM, Cohen DM.

Head Neck Pathol. 2021 Jun;15(2):572-587. doi: 10.1007/s12105-020-01262-9. Epub 2021 Jan 7.

The many diverse terms used to describe the wide spectrum of changes seen in proliferative verrucous leukoplakia (PVL) have resulted in disparate clinical management. The objective of this study was to produce an expert consensus guideline for standardized assessment and reporting by pathologists diagnosing PVL related lesions. 299 biopsies from 84 PVL patients from six institutions were selected from patients who had multifocal oral leukoplakic lesions identified over several years (a minimum follow-up period of 36 months). The lesions demonstrated the spectrum of histologic features described in PVL, and in some cases, patients developed oral cavity squamous cell carcinoma (SCC). An expert working group of oral and maxillofacial and head and neck pathologists reviewed microscopic features in a rigorous fashion, in combination with review of clinical photographs when available. The working group then selected 43 single slide biopsy cases for whole slide digital imaging (WSI) review by members of the consensus conference. The digital images were then reviewed in two surveys separated by a washout period of at least 90 days. Five non-PVL histologic mimics were included as controls. Cases were re-evaluated during a consensus conference with 19 members reporting on the cases. The best inter-observer diagnostic agreement relative to PVL lesions were classified as “corrugated ortho(para)hyperkeratotic lesion, not reactive” and “SCC” (chi-square p = 0.015). There was less than moderate agreement (kappa < 0.60) for lesions in the “Bulky hyperkeratotic epithelial proliferation, not reactive” category. There was ≥ moderate agreement (> 0.41 kappa) for 35 of 48 cases. This expert consensus guideline has been developed with support and endorsement from the leadership of the American Academy of Oral and Maxillofacial Pathology and the North American Society of Head and Neck Pathologists to recommend the use of standardized histopathologic criteria and descriptive terminology to indicate three categories of lesions within PVL: (1) “corrugated ortho(para)hyperkeratotic lesion, not reactive;” (2) “bulky hyperkeratotic epithelial proliferation, not reactive;” and (3) “suspicious for,” or “squamous cell carcinoma.” Classification of PVL lesions based on a combination of clinical findings and these histologic descriptive categories is encouraged in order to standardize reporting, aid in future research and potentially guide clinical management.

PubMed ID: 33415517

Article Size: 2.33 MB

Berdugo J, Thompson LDR, Purgina B, Sturgis CD, Tuluc M, Seethala R, Chiosea SI.

Head Neck Pathol. 2019 Jun;13(2):154-161.
doi: 10.1007/s12105-018-0925-3. Epub 2018 Apr 26.

The 8th edition of American Joint Committee on Cancer (AJCC 8th) staging manual incorporated depth of invasion (DOI) into pT stage of oral cavity cancer. The aim of this study was to characterize several histological findings that may complicate measurement of DOI in early conventional squamous cell carcinomas (SCC) of the oral tongue: (1) lack of or minimal residual carcinoma following biopsy; (2) positive deep margin; (3) extratumoral perineural invasion (PNI); and (4) lymphatic or vascular invasion. Conventional SCC of the oral tongue (n = 407) with the largest dimension of ≤ 4 cm and with a negative elective cervical lymph node dissection (pN0) were reviewed. A clear plastic ruler was used to measure DOI by dropping a “plumb line” to the deepest point of the invasive tumor from the level of the basement membrane of the normal mucosa closest to the invasive tumor. Examples of identifying reference point on the mucosal surface of oral tongue from which to measure the DOI are illustrated. In the experience of one contributing institution, the residual carcinoma was absent in 14.2% of glossectomies (34/239), while in 4.8% of cases (10/205) there was only minimal residual carcinoma. In 11.5% (21/183) of pT2 cases the deep margin was positive and thus DOI and pT may be underestimated. Of all cases with PNI, extratumoral PNI was identified in 23.1% (31/134) of cases, but represented the deepest point of invasion in only two cases. In one case, lymphatic invasion represented the deepest point of invasion and could have led to upstaging from pT1 to pT2. In conclusion, DOI measurement for SCC of the oral tongue may require re-examination of the diagnostic biopsy in up to 20% of cases due to the absence or only minimal residual carcinoma in glossectomy specimens. In 11.5% of apparently pT2 cases, DOI may be underestimated due to the positive deep margin. Rarely, extratumoral PNI or lymphatic invasion may be the deepest point of invasion. Overall, two issues (absent or minimal residual disease and positive deep margin) may confound DOI measurement in early SCCs of oral tongue.

PubMed ID: 29700721

Article Size: 3 MB

Deng F, Thompson LDR, Lai J.

Head Neck Pathol 2022 Jun;16(2):544-549. doi: 10.1007/s12105-021-01348-y.

Syphilis is a sexually transmitted infectious disease caused by Treponema pallidum and characterized by a complex and variable clinical presentation. Cases of unexpected oral syphilis presenting as non-healing ulcers are uncommonly reported. We report 3 cases (one female and two males, aged 35, 35, and 56 years, respectively) in which patients presented with non-healing oral ulcers. Biopsies revealed surface ulceration and a significant neutrophilic infiltrate rather than the more conventional plasma cell infiltrate seen with most reported syphilis infections, potentially leading to an inaccurate diagnosis. Treponema pallidum immunohistochemistry highlighted spirochetes within the epithelium, with additional diagnostic confirmation by serum T. pallidum particle agglutination assay. Sexual history documentation by the clinician with nonspecific oral ulcers is paramount to aiding diagnosis and leading to proper management. Further, it is important to perform immunohistochemistry for T. pallidum in oral biopsies from non-healing ulcers, especially when clinical history raises the differential diagnosis or when other clinical manifestations may support this consideration.

PubMed ID: 34342809

Article Size: 2 MB

Prabhu AV, Sturgis CD, Lai C, Maxwell JH, Merzianu M, Hernandez-Prera JC, Purgina B, Thompson LDR, Tuluc M, Yang X, Seethala RR, Ferris RL, Chiosea SI.

Oral Oncol. 2017 Dec;75:184-188.

OBJECTIVES: To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue.

MATERIALS AND METHODS: Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n=124), TBM were obtained before examination of the glossectomy specimen.

RESULTS AND CONCLUSIONS: Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32% sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface.

PubMed ID: 29074194

Article Size: <1 MB

 

Upadhyaya JD, Fitzpatrick SG, Cohen DM, Bilodeau EA, Bhattacharyya I, Lewis JS Jr, Lai J, Wright JM, Bishop JA, Leon ME, Islam MN, Seethala R, Padilla RJ, Carlos R, Müller S, Thompson LDR.

Head Neck Pathol. 2020 Mar;14(1):156-165. doi: 10.1007/s12105-019-01035-z. Epub 2019 Apr 10.

The use of diverse terminology may lead to inconsistent diagnosis and subsequent mistreatment of lesions within the proliferative verrucous leukoplakia (PVL) spectrum. The objectives of this study were: (a) to measure inter-observer variability between a variety of pathologists diagnosing PVL lesions; and (b) to evaluate the impact of diverse terminologies on understanding, interpretation, and subsequent treatment planning by oral and maxillofacial surgeons (OMFS). Six oral pathologists (OP) and six head and neck pathologists (HNP) reviewed 40 digitally scanned slides of PVL-type lesions. Inter-observer agreement on diagnoses was evaluated by Fleiss’ kappa analysis. The most commonly used diagnostic terminologies were sent to ten OMFS to evaluate their resulting interpretations and potential follow-up treatment approaches. The overall means of the surgeons’ responses were compared by Student t test. There was poor inter-observer agreement between pathologists on the diagnosis of PVL lesions (κ = 0.270), although there was good agreement (κ = 0.650) when diagnosing frankly malignant lesions. The lowest agreement was in diagnosing verrucous hyperplasia (VH) with/without dysplasia, atypical epithelial proliferation (AEP), and verrucous carcinoma (VC). The OMFS showed the lowest agreement on identical categories of non-malignant diagnoses, specifically VH and AEP. This study demonstrates a lack of standardized terminology and diagnostic criteria for the spectrum of PVL lesions. We recommend adopting standardized criteria and terminology, proposed and established by an expert panel white paper, to assist pathologists and clinicians in uniformly diagnosing and managing PVL spectrum lesions.

PubMed ID: 30972634

Article Size: 2.2 MB

Darling MR, Hwang JTK, Dickson BJ, Cutz JC, Salama S, McCord C, Pritzker KPH, Mock D, Thompson LDR.

Appl Immunohistochem Mol Morphol. 2023 Jul 1;31(6):399-405.

While a 3-tier oral epithelial dysplasia grading system has been utilized for decades, it is widely recognized as a suboptimal risk indicator for transformation to cancer. A 2-tier grading system has been proposed, although not yet validated. In this study, the 3-tier and 2-tier dysplasia grading systems, and an S100A7 immunohistochemical signature-based grading system were compared to assess prediction of risk of transformation to oral cancer. Formalin-fixed, paraffin-embedded biopsy specimens with known clinical outcomes were obtained retrospectively from a cohort of 48 patients. Hematoxylin and eosin-stained slides were used for the 2- and 3-tier dysplasia grading, while S100A7 for biomarker signature-based assessment was based on immunohistochemistry. Inter-observer variability was determined using Cohen’s kappa (K) statistic with Cox regression disease free survival analysis used to determine if any of the methods were a predictor of transformation to oral squamous cell carcinoma. Both the 2- and 3-tier dysplasia grading systems ranged from slight to substantial inter-observer agreement (Kw between 0.093 to 0.624), with neither system a good predictor of transformation to cancer (at least P=0.231; (P>>>0.05). In contrast, the S100A7 immunohistochemical signature-based grading system showed almost perfect inter-observer agreement (Kw=0.892) and was a good indicator of transformation to cancer (P=0.047 and 0.030). The inherent grading challenges with oral epithelial dysplasia grading systems and the lack of meaningful prediction of transformation to carcinoma highlights the significant need for a more objective, quantitative, and reproducible risk assessment tool such as the S100A7 immunohistochemical signature-based system.

PubMed ID: 37249075

Article Size: 0.5 MB

Thompson LDR, Koh SS, Lau SK.

Head Neck Pathol. 2020 Sep;14(3):571-576. doi: 10.1007/s12105-019-01071-9. Epub 2019 Sep 4.

Schwannomas commonly occur in the head and neck but infrequently involve the oral cavity and rarely affect the tongue. The clinical and pathologic features of 19 cases of schwannoma arising in the tongue were analyzed. There were 13 males and 6 females ranging in age from 12 to 82 years (mean 34 years; median 29 years). The majority of tumors presented as an asymptomatic mass localized to the anterior two-thirds of the tongue. Histologically, 18 schwannomas exhibited characteristic Antoni A and B areas with the former pattern predominating. One tumor was composed exclusively of cellular Antoni A tissue and was classified as a cellular schwannoma. Tumor encapsulation was variable with nearly half of the lesions lacking a well-defined fibrous capsule. All were strongly and diffusely positive for S-100 protein. No recurrences were observed on clinical follow-up. Schwannoma of the tongue, although rare, should be separated from other types of lingual nerve sheath proliferations and tumors.

PubMed ID: 31485983

Article Size: 2.2 MB

Dickson BC, Antonescu CR, Argyris PP, Bilodeau EA, Bullock MJ, Freedman PD, Gnepp DR, Jordan RC, Koutlas IG, Lee CH, Leong I, Merzianu M, Purgina BM, Thompson LDR, Wehrli B, Wright JM, Swanson D, Zhang L, Bishop JA.

Am J Surg Pathol. 2018 Oct;42(10):1297-1305.

Ectomesenchymal chondromyxoid tumor is a rare and benign neoplasm with a predilection for the anterior dorsal tongue. Despite morphologic heterogeneity, most cases are characterized by a proliferation of bland spindle cells with a distinctive reticular growth pattern and myxoid stroma. The immunophenotype of these neoplasms is likewise variable; most cases express glial fibrillary acid protein and S100 protein, with inconsistent reports of keratin and myoid marker expression. The molecular pathogenesis is poorly understood; however, a subset of cases has been reported to harbor EWSR1 gene rearrangement. Following identification of an RREB1-MKL2 fusion gene by RNA Sequencing in an index patient, a retrospective review of additional cases of ectomesenchymal chondromyxoid tumors was performed to better characterize the clinical, immunohistochemical, and molecular attributes of this neoplasm. A total of 21 cases were included in this series. A marked predisposition for the dorsal tongue was confirmed. Most cases conformed to prior morphologic descriptions; however, hypercellularity, hyalinized stroma, and necrosis were rare attributes not previously emphasized. The neoplastic cells frequently coexpressed glial fibrillary acid protein, S100 protein, keratin, smooth muscle actin, and/or desmin; a single case was found to contain significant myogenin expression. An RREB1-MKL2 fusion product was identified in 19 tumors (90%), a single tumor (5%) had an EWSR1-CREM fusion product, and the remaining case lacked any known fusion gene by RNA Sequencing. The latter 2 cases subtly differed morphologically from many in the cohort. This series illustrates that recurrent RREB1-MKL2 fusions occur in most, perhaps all, cases of ectomesenchymal chondromyxoid tumor.

PubMed ID: 29912715

Article Size: 1 MB

 

Agaimy A, Mueller SK, Harrer T, Bauer S, Thompson LDR.

Head Neck Pathol. 2018 Dec;12(4):511-516.

Kaposi sarcoma (KS) of the head and neck area is uncommon with limited published case series. Our routine and consultation files were reviewed for histologically and immunohistochemically proven KS affecting any cutaneous or mucosal head and neck site. Ten males and one female aged 42-78 years (median, 51 years; mean, 52 years) were retrieved. Eight patients were HIV-positive and three were HIV-negative. The affected sites were skin (n = 5), oral/oropharyngeal mucosa (n = 5), and lymph nodes (n = 3) in variable combination. The ear (pinna and external auditory canal) was affected in two cases; both were HIV-negative. Multifocal non-head and neck KS was reported in 50% of patients. At last follow-up (12-94 months; median, 46 months), most of patients were either KS-free (n = 8) or had ongoing remission under systemic maintenance therapy (n = 2). One patient was alive with KS (poor compliance). Histopathological evaluation showed classical features of KS. One case was predominantly sarcomatoid with prominent inflammation mimicking undifferentiated sarcoma. Immunohistochemistry showed consistent expression of CD31, CD34, ERG, D2-40 and HHV8 in all cases. This is one of the few series devoted to head and neck KS showing high prevalence of HIV-positivity, but also unusual presentations in HIV-negative patients with primary origin in the skin of the ear and the auditory canal. KS should be included in the differential diagnosis of difficult-to-classify spindle cell lesions at this uncommon location.

PubMed ID: 29508130

Article Size: 1.6 MB

 

Sridharan S, Thompson LDR, Purgina B, Sturgis CD, Shah AA, Burkey B, Tuluc M, Cognetti D, Xu B, Higgins K, Hernandez-Prera JC, Guerrero D, Bundele MM, Kim S, Duvvuri U, Ferris RL, Gooding WE, Chiosea SI.

Cancer. 2019 Sep 15;125(18):3198-3207. doi: 10.1002/cncr.32199. Epub 2019 Jun 7.

BACKGROUND: The eighth edition of the American Joint Committee on Cancer staging manual (AJCC8) added depth of invasion to the definition of pathologic T stage (pT). In the current study, the authors assess pT stage migration and the prognostic performance of the updated pT stage and compare it with other clinicopathologic variables in patients with early squamous cell carcinoma of the oral tongue (OTSCC; tumors measuring ≤4 cm) with histologically benign lymph nodes (pN0).

METHODS: A multi-institutional cohort of patients with early OTSCC was restaged as per AJCC8. Primary endpoints were local recurrence (LR) and locoregional recurrence (LRR). Influential variables were identified and an LR/LRR prediction model was developed.

RESULTS: There were a total of 494 patients, with 49 LR and 73 LRR. AJCC8 pT criteria resulted in upstaging of 37.9% of patients (187 of 494 patients), including 34.5% (64 of 185 patients) from pT2 to pT3, without improving the prognostication for LR or LRR. Both LR and LRR were found to be similar for patients with AJCC8 pT2 and pT3 disease. On multivariate analysis, LR was only found to be associated with distance to the closest margin (hazard ratio, 0.36; 95% CI, 0.20-0.64 [P = .0007]) and perineural invasion (hazard ratio, 1.92; 95% CI, 1.10-0.64 [P = .046]). Based on these 2 predictors, a final proportional hazards regression model (which may be used similar to a nomogram) was developed. The proposed model appeared to be superior to AJCC pT stage for estimating the probability of LR and LRR for individual patients with early OTSCC.

CONCLUSIONS: AJCC8 pT criteria resulted in pT upstaging of patients with pN0 disease without improved LR or LRR prognostication. The proposed model based on distance to the closest margin and perineural invasion status outperformed pT as a predictor of LR and LRR in patients with early OTSCC.

PubMed ID: 31174238

Article Size: <1 MB

Nelson BL, Thompson LDR.

Head Neck Pathol. 2019 Mar;13(1):1-3. doi: 10.1007/s12105-019-01007-3. Epub 2019 Jan 29.

FIRST PARAGRAPH: Nearly all surgical pathologists will encounter oral mucosal biopsies in their day to day practice. Many of these biopsies are fraught with diagnostic difficulty and may be challenging, usually due to inadequate clinical information, an unfamiliarity with anatomic landmarks and/or terminology used by the submitting physician or dentist, and the often limited size of the sample. A clinical description and history to accompany the submitted biopsy is often essential to the proper diagnosis and subsequent treatment of many oral conditions. A clinical history is a requirement recognized by the College of American Pathologist (CAP). The value and utility of a clinical history in the practice of pathology is undisputed. However, between 5.9 and 8.4% of cases submitted for pathologic review have no clinical history, or include vague information like “lesion,” “bump” or “ulcer.” Often the exact anatomic site is not included, stating only “oral cavity,” or “soft tissue” without any further designation as to exact anatomic site. This lack of important information may result in less than ideal interpretations. Additionally, concise clinical histories have been associated with shorter sign-out turnaround times. Pathologists find it too difficult to communicate with providers to obtain additional clinical information, claiming they are not in the office, they don’t return messages, or clinicians are too busy to be bothered. With nearly ubiquitous access to photography, the old adage, “A picture is worth a thousand words,” would seem to go a long way towards providing further clinical information. The clinical appearance, with the various nuances of color, texture and location are well suited to clinical photography. Cerroni et al., studied the utility of submitting clinical photographs with biopsy requests to dermatopathologists. The study showed that clinical photographs facilitated better pathology interpretation. Further, Ferrara et al., highlighted that clinical photographs do not introduce bias into the diagnosis of melanocytic lesion of the skin. There is a long held misconception by many physicians and dentists that clinically describing the sampled lesion unduly biases the pathologist: how patently false. Clear and concise clinical descriptions of mucosal lesions are essential to developing an appropriate differential diagnosis and a subsequent accurate interpretation. In an effort to highlight the importance of these characteristics, the topics covered by the contributing authors to this special issue have been divided by color, texture and location.

PubMed ID: 30693461

Article Size: <1 MB

Thompson LDR, Koh SS, Lau SK.

2020 Jun;14(2):374-380. doi: 10.1007/s12105-019-01041-1. Epub 2019 May 20.

Neurofibromas rarely occur within the oral cavity and infrequently involve the tongue. The majority of lingual neurofibromas arise in patients affected by neurofibromatosis type 1 (NF1). Neurofibromas of the tongue unassociated with this disorder are exceedingly uncommon. The clinical and pathologic features of 10 cases of sporadic lingual neurofibromas, unassociated with NF1, were evaluated. The patients included six females and four males ranging in age from 30 to 69 years (mean 59 years; median 63 years). An asymptomatic or slowly enlarging lingual mass was the most common clinical presentation. None of the patients were documented to have NF1. Histologically, the tumors were unencapsulated and situated beneath an intact squamous mucosa. The tumors are comprised of spindle cells with wavy nuclei within a collagenous to myxoid stroma. One tumor was characterized by a plexiform growth pattern. The lesional cells were positive for S-100 protein. Clinical follow up, available for all patients, showed no recurrences and no subsequent development of additional clinical manifestations of NF1. Lingual neurofibromas should be distinguished from other peripheral nerve sheath tumors that can affect this anatomic site. This series of cases confirms that sporadic neurofibromas of the tongue may be rarely encountered in patients having no other features of NF1.

PubMed ID: 31111316

Article Size: 2.7 MB

Lau SK, Bishop JA, Thompson LD.

Head Neck Pathol. 2015 Jun;9(2):253-9.

Spindle cell lipoma is a histologically distinct variant of lipoma characteristically arising in the subcutis of the posterior neck, upper back, or shoulder. Spindle cell lipomas infrequently occur within the oral cavity and, in particular, rarely involve the tongue. The clinical and pathologic features of eight cases of spindle cell lipoma affecting the tongue were analyzed. The study group included five men and three women ranging in age from 35 to 80 years (mean 57.4 years). Most lesions presented as either a painless or slowly growing lingual mass. The tumors were well circumscribed and characterized microscopically by a mixture of mature adipocytes, cytologically bland spindle cells, and interspersed bundles of thick collagen fibers in variable proportions. Myxoid stroma was a prominent feature in three lesions. The spindle cells were positive with CD34, while negative with S-100 protein, desmin, and smooth muscle actin. Treatment consisted of local excision in all cases. There have been no recurrences to date, with clinical follow up information available for all patients (range 11-118 months; mean 50.8 months). Lingual examples of spindle cell lipoma should be distinguished from other fat containing spindle cell neoplasms that can arise at this anatomic site.

PubMed ID: 25319950

Article Size: 2 MB

 

Diapera MJ, Lozon CL, Thompson LD.

Am J Otolaryngol. 2009 Mar-Apr;30(2):101-5.

BACKGROUND: Extra-urogenital tract malacoplakia is uncommon, with tongue malacoplakia being exceptionally rare. The nonspecific clinical presentation and variable histologic patterns can make recognition of this lesion and separation from other lesions challenging. There are only a few reported cases in the English literature.

MATERIALS AND METHODS: Five case reports of tongue malacoplakia were compiled from the literature (MedLine 1960-2008) and integrated with this case report.

RESULTS: The patients included 4 males and 2 females, ranging in age from 9 to 98 years (mean, 64 years). Patients presented with difficulty swallowing, foreign body sensation, a mass lesion, or referred pain (neck or ear). Symptoms were present from a few days up to 18 months. The base of the tongue was the most frequent site, although midline tongue and half of the tongue were also affected. Radiographic studies demonstrated a mass, with a single lesion showing positron emission tomography positivity. Two patients had previous cancers (prostate and colorectal; larynx). This case report was a farm hand for horses, with gram-negative rods, suggestive of Rhodococcus equi identified. The lesions were 1 to 2 cm in greatest dimension. Histologically, there is pseudoepitheliomatous hyperplasia or ulceration with a heavy acute and chronic inflammatory infiltrate. The subepithelial spaces are completely filled with eosinophilic histiocytes, most of which contain granular material in their cytoplasm. Well-formed, blue, calcific bodies are noted, a few showing a ‘targetoid appearance’ and concentric lamination. These Michaelis-Gutmann bodies are positive with von Kossa, iron, and periodic acid-Schiff stains. These findings support a diagnosis of malacoplakia. The differential diagnosis includes granular cell tumor, poorly differentiated carcinoma, and Langerhans histiocytosis. Patients are managed with antibiotic therapy and excision.

CONCLUSIONS: Tongue malacoplakia is rare, often presenting as a mass lesion. Histologic recognition of this abnormal phagocytic disorder will prevent potentially disfiguring surgery.

PubMed ID: 19239951

Article Size: 3 MB

 

Argyris PP, Reed RC, Manivel JC, Lopez-Terrada D, Jakacky J, Cayci Z, Tosios KI, Pambuccian SE, Thompson LD, Koutlas IG.

Head Neck Pathol. 2013 Mar;7(1):40-9.

Alveolar soft part sarcoma (ASPS) constitutes a rare soft tissue malignant neoplasm comprising less than 1 % of all soft tissue sarcomas. ASPS demonstrates a strong predilection for adolescents and young adults, with a female predominance reported. The head and neck region is the most commonly affected region in pediatric patients with the tongue and orbit affected most commonly. Herein we present the clinical, radiographic, histopathologic, immunohistochemical and molecular features of two examples of ASPS affecting the oral cavity of 4 and 13 year-old boys, along with a focused review of the literature on intraoral ASPS in pediatric patients.

PubMed ID: 22961078

Article Size: <1 MB

 

Suárez C, Barnes L, Silver CE, Rodrigo JP , Shah JP, Triantafyllou A, Rinaldo A, Cardesa A, Pitman KT, Kowalski LP, Robbins KT , Hellquist H, Medina JE, de Bree R, Takes RP, Coca-Pelaz A , Bradley PJ, Gnepp DR, Teymoortash A, Strojan P, Mendenhall WM, Anderson Eloy J, Bishop JA, Devaney KO, Thompson LDR, Hamoir M, Slootweg PJ, Vander Poorten VV, Williams MD, Wenig BM, Skálová A, Ferlito A.

Auris Nasus Larynx. 2016 Oct;43(5):477-484.

The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0–14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.

PubMed ID: 27017314

Article Size: <1 MB

 

Gaiger de Oliveira M, Thompson LD, Chaves AC, Rados PV, da Silva Lauxen I, Filho MS.

Ann Diagn Pathol. 2004 Aug;8(4):207-12.

Melanotic neuroectodermal tumor of infancy is a rare congenital neoplasm involving the head and neck in young patients. The clinical assessment, histologic diagnosis, and management is reviewed, with an emphasis on different treatment alternatives in two new case reports.

PubMed ID: 15290671

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Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):538S-539S. doi: 10.1177/0145561319890154.

FIRST PARAGRAPH: There has been a recent reemergence in the development of oral syphilis, a sexually transmitted infection caused by the Treponema pallidum subspecies pallidum spirochaeta bacterium, with oral manifestations dependent on stage at presentation (early: primary, secondary, early latent; late: late latent, tertiary). Oral sex has contributed to the overall increase in disease spread, with the highest incidence in 25- to 29-yearold males (88% of oral cases documented in males, especially in males who have sex with males). Concurrent infections with HIV or other sexually transmitted infections are common. The lips, tongue, and palate are most commonly infected, while tonsils and gingiva may also be affected. Early primary presentation is of a painless, usually solitary ulcer (chancre) which forms about 3 weeks after inoculation (Figure 1). Early secondary presentation is about 3 to 12 weeks after chancre resolution and is the stage most oral syphilis is diagnosed. There are mucous white patches, sometimes multifocal. Condyloma lata is a papillary lesion. Latent syphilis is considered inactive disease, with serologic proof of infection, but without disease symptoms, usually >1 year after secondary syphilis. Tertiary syphilis may develop anywhere up to 15 years after initial infection, showing gumma (granulomatous inflammation) of the palate and/or tongue with atrophic luetic glossitis. Congenital manifestations are rare (screwdriver-shaped incisors and mulberry molars). Treatment involves intramuscular penicillin injections with appropriate counseling and screening for other sexually transmitted diseases.

PubMed ID: 31760793

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Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):536S-537S. doi: 10.1177/0145561319890175.

FIRST PARAGRAPH: Odontomas are hamartomas of odontogenic epithelium and ectomesenchyme, separated into compound and complex types. Both considered as a developmental anomaly, compound odontomas show diminutive tooth-like structures (Figures 1A and 2A), while complex odontomas show a haphazard aggregate of enamel and dentin (Figures 1B and 2B). Odontomas are considered to be one of the most common odontogenic tumors, with most presenting in the first 2 decades of life without sex predilection. Compound odontomas are more common in the anterior maxilla, while complex odontomas are more common in the posterior mandible (Figure 1B). The lesions are usually asymptomatic, detected on routine dental imaging studies, with a few cases reported in Rubinstein-Taybi syndrome. Radiographic features are considered diagnostic, with tooth-shaped structures surrounded by a radiolucent zone in compound odontomas versus a radiodense mass with a radiolucent zone seen in complex odontoma. Simple excision is curative without risk of recurrence.

PubMed ID: 31760790

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Thompson LD.

Ear Nose Throat J. 2015 Jan;94(1):22-4.

FIRST PARAGRAPH: Cherubism is an autosomal-dominant inherited disease with variable expression. It is characterized by a progressive, painless, and symmetric expansion of the jaws. The disease is caused by a point mutation in the SH3BP2 gene (chromosome 4p16.3), which leads to dysregulation of the Msx-1 gene; this gene is involved in regulating mesenchymal interaction in craniofacial morphogenesis.

PubMed ID: 25606831

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Thompson LD.

Ear Nose Throat J. 2013 Jul;92(7):288-90.

FIRST PARAGRAPHS: Osteosarcoma affects the mandible and the maxilla differently, with mandibular tumors tending to arise from the body of the mandible while maxillary tumors arise from the alveolar ridge and sinus. Osteosarcoma is a mesenchymal malignancy in which the neoplastic cells synthesize and secrete the organic components of bone matrix. While it is the most common primary tumor of bone, it is very uncommon overall.

PubMed ID: 23904301

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Thompson LD.

Ear Nose Throat J. 2011 Nov; 90(11):518-34.

FIRST PARAGRAPH: A traumatic ulcer is a chronic traumatic ulceration of the oral mucosa that shows unique histopathologic features. Also known as traumatic granuloma, eosinophilic granuloma, and Riga-Fede disease, this lesion is usually caused by some sort of mechanical injury. The most common causes include accidental trauma from biting, malposed teeth, and even sharp foodstuffs. However, self inflicted wounds caused by nocturnal clenching or tongue and lip biting, electrical and thermal injuries, hot foods or beverages, and even factitial injuries yield a similar finding. Ulceration of the ventral tongue as a result of tongue thrusting in infants with natal or neonatal teeth is referred to as Riga-Fede disease.

PubMed ID: 22109918

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Thompson LD.

Ear Nose Throat J. 2014 Sep;93(9):386-8.

FIRST PARAGRAPH: Keratocystic odontogenic tumor (KCOT; formerly known as odontogenic keratocyst) is a distinct developmental odontogenic cyst that may be locally aggressive and may be part of the nevoid basal cell carcinoma syndrome (NBCCS, or Gorlin syndrome). Inherited as an autosomal dominant trait, there is high penetrance, although with variable expression, associated with loss of function of the PTCH gene (chromosome 9q22.3-q31), a tumor suppressor gene.

PubMed ID: 25255344

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Thompson LD.

Ear Nose Throat J. 2003 Jan;82(1):19.

FIRST PARAGRAPH: Ameloblastomas are locally aggressive gnathic tumors that have a high propensity for recurrence. They are believed to arise from remnants of the odontogenic epithelium or the developing enamel organ. They occur in patients over a wide spectrum of ages and equally among the sexes, as a slow-growing, often asymptomatic, locally invasive tumor. Radiographic images usually demonstrate a multilocular, expansile radiolucency of bone, usually of the posterior mandible.

PubMed ID: 12610896

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Nelson BL, Thompson LD.

Ear Nose Throat J. 2003 Apr;82(4):259.

FIRST PARAGRAPH: Fibrous dysplasia (fibro-osseous metaplasia) is one of a diverse group of diseases that are characterized by alterations in bone growth. It is a developmental, tumor-like process of unknown etiology. Its initial clinical sign is usually a painless enlargement of the affected bone. It occurs in equal proportions in males and females, most often during the first two decades of life.

PubMed ID: 12735156

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Nelson BL, Thompson LD.

Head Neck Pathol. 2010 Dec;4(4):290-1.

A case of compound odontomas of the anterior maxilla is discussed. Multiple tooth like structures were discovered upon surgical excision.

PubMed ID: 20533004

Article Size: <1 MB

 

Thompson, LD.

Ear Nose Throat J. 2018 Mar;97(3):57.

FIRST PARAGRAPH: A dentigerous cyst is a development cyst that surrounds and envelops the crown of an unerupted tooth, attached at the crown-root (cemento-enamel or cervical) junction. Dentigerous cysts account for about 20% of all odontogenic cysts, developing during a peak age of 10 to 30 years, with a male predilection (3:2). The lesion presents in the mandible (3rd molar region) about twice as often as the maxilla (near maxillary canines).

PubMed ID: 29554396

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Thompson LD.

Ear Nose Throat J. 2017 Jul;96(7):240.

FIRST PARAGRAPH: Lobular capillary hemangioma (LCH), sometimes also called pyogenic granuloma or epulis gravidarum, is a benign overgrowth of capillaries showing a vascular phenotype. There are several etiologic factors, including hormones (increased in pregnancy and in patients using oral contraceptives), localized trauma (biting, fractured tooth, poor restorations), and when there is poor oral hygiene.

PubMed ID: 28719705

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Nelson BL, Thompson L.

Ear Nose Throat J. 2007 Oct;86(10):600-1

FIRST PARAGRAPH: Median rhomboid glossitis — also known as central papillary atrophy and posterior midline atrophic candidiasis — is a type of erythematous candidiasis unique to the midline posterior tongue. It occurs in as many as 1% of adults.

PubMed ID: 17990677

Article Size: <1 MB

Nelson BL, Thompson LD.

Ear Nose Throat J. 2006 Jun;85(6):365.

FIRST PARAGRAPH: Melanotic neuroectodermal tumor of infancy is a rare, neural-crest-derived neoplasm that is believed to be congenital. The tumor has a marked predilection for the head and neck — particularly the maxilla, where approximately 70% of these tumors are located. The anterior maxilla is most commonly affected. There is no predilection for either sex. Nearly all patients present with an enlarging mass, usually within a few years of birth. Intraoral lesions may appear ‘blue,’ suggesting the presence of pigment. Radiographic images will often show a destructive lesion with tooth displacement, but they are nonspecific. Laboratory studies show high urinary levels of vanillylmandelic acid.

PubMed ID: 16866106

Article Size: <1 MB

Penner CR, Thompson LD.

Ear Nose Throat J. 2003 Jul;82(7):493-4.

FIRST PARAGRAPH: Necrotizing sialometaplasia is a benign, self-limited, reactive inflammatory process that involves salivary glands. It occurs in middle-aged patients; men are affected slightly more often than women. Patients may experience an antecedent event (e.g., surgery, radiation, or trauma) up to 3 weeks before necrotizing sialometaplasia appears clinically, but many are asymptomatic. A submucosal nodular swelling will give way to an ulcerative, crater-like lesion that usually measures less than 3 cm in its greatest dimension.

PubMed ID: 12955830

Article Size: <1 MB

Nelson BL, Thompson LD.

Ear Nose Throat J. 2004 Jan;83(1):22.

FIRST PARAGRAPH: Cicatricial pemphigoid is a vesiculobullous disease of the skin that may be found in the oral cavity. Previously designated ‘benign mucous membrane pemphigoid,’ cicatricial pemphigoid is a chronic, blistering, autoimmune disease that affects mucous membranes. Tissue-bound autoantibodies are directed against one or more components of the basement membrane in an affected individual. Cicatricial pemphigoid initially occurs in the fifth to seventh decades of life, and it is observed more frequently in women. Patients usually describe oral pain and/or ulceration, often of many years’ duration. Clinically, the disease is characterized by the formation of bullae, which can be found anywhere in the oral cavity. The bullae rupture and produce ulceration, which may cause a scar (cicatrix) upon healing.

PubMed ID: 14986753

Article Size: <1 MB

Gannon FH, Thompson L.

Ear Nose Throat J. 2004 Jul;83(7):458.

FIRST PARAGRAPH: Ossifying fibroma of the jaw is a benign, fibro-osseous lesion that is part of a larger family of fibro-osseous lesions that includes juvenile active ossifying fibroma, psammomatous ossifying fibroma, and extragnathic ossifying fibroma of the skull. Ossifying fibromas of the jaw are well-circumscribed, slowly growing lesions. They are often mentioned in the same differential diagnosis as fibrous dysplasia, but it is important to make the distinction because the former lends itself to ready enucleation, while the latter can be admixed with surrounding tissues, making surgery more complicated.

PubMed ID: 15372914

Article Size: <1 MB