Category Archives: Oropharynx

Thompson LDR, Burchette R, Iganej S, Bhattasali O.

Head Neck Pathol. 2020 Sep;14(3):666-688. doi: 10.1007/s12105-019-01096-0. Epub 2019 Nov 18.

This study evaluates the prognostic impact of several factors in oropharyngeal squamous cell carcinoma (OPSCC), controlling for human papillomavirus (HPV)-associated tumors and stage (American Joint Committee on Cancer 8th edition). All patients in Southern California Permanente Medical Group diagnosed with OPSCC between 2006 and 2012 tested for p16 immunohistochemistry were included. Review of all pathology materials was combined with central p16 testing. Multivariable analyses were performed. The cohort of 390 patients included 342 p16-positive and 48 p16-negative tumors. For all-comers, on univariate analysis, the following factors, when present, were associated with improved patient survival: p16-positive tumor (n = 324, p < 0.001); crypt versus surface tumor location (n = 312, p = 0.004); nonkeratinizing type (n = 309, p < 0.0001); nonkeratinizing with maturation type (n = 37, p < 0.0001); basaloid pattern (n = 284, p = 0.005); and a broad, pushing border of infiltration (n = 282, p = 0.004). Inferior survival outcomes were observed with: age ≥ 55 years (p < 0.0001); ≥ 10 pack-year smoking history (n = 183, p = 0.003); increasing tumor stage (p < 0.0001); overt radiographic extranodal extension (ORENE) (n = 58, p < 0.0001); low level IV/Vb lymph node involvement (n = 45, p = 0.0002); a jagged pattern of infiltration (n = 76, p = 0.0004); tumor ulceration (n = 76, p = 0.0004); absent lymphocytic infiltrate (p < 0.0001); and concurrent dysplasia (n = 125, p = 0.009). On multivariable analysis, accounting for patient age, smoking history ≥ 10 pack-years, and TNM stage, for patients with p16-positive disease, advanced TNM stage (p = 0.007), the presence of ORENE (p = 0.0002), and low-neck lymphadenopathy (p = 0.0001) were independent negative prognostic factors for disease free survival (DFS). Older age (p < 0.0001), smoking history ≥ 10 pack-years (p = 0.02), advanced TNM stage (p = 0.0002), ORENE (p = 0.004), and low-neck lymphadenopathy (p = 0.002) were independent negative prognostic factors for OS. Among patients with p16-positive OPSCC, older age, smoking history, advanced stage, ORENE, and low-neck lymphadenopathy were significant negative prognostic factors for DFS and/or OS. Further refinement of staging to incorporate additional lymph node findings may be warranted.

PubMed ID: 31741151

Article Size: 11 MB

Koyuncu CF, Lu C, Bera K, Zhang Z, Xu J, Andrea Toro Castaño P, Corredor G, Chute D, Fu P, Thorstad WL, Faraji F, Bishop JA, Mehrad M, Castro PD, Sikora AG, Thompson LDR, Chernock RD, Lang Kuhs KA, Luo J, Sandulache VC, Adelstein DJ, Koyfman S, Lewis JS Jr, Madabhushi A.

J Clin Invest. 2021 Apr 15;131(8):e145488. doi: 10.1172/JCI145488.

BACKGROUND: p16 positive oropharyngeal squamous cell carcinoma (OPSCC) patients are potentially cured with definitive treatment. However, there are currently no reliable biomarkers of treatment failure in p16 positive OPSCC. Pathologist-based visual assessment of tumor cell multinucleation has been shown to be independently prognostic of disease-free survival in p16 positive OPSCC. However, its quantification is time-intensive, subjective, and at risk of interobserver variability.

METHODS: We present a deep learning-based metric, the multi-nucleation index (MuNI), for prognostication in p16 positive OPSCC. This approach quantifies tumor multi-nucleation from digitally scanned hematoxylin eosin (H&E)-stained slides. Representative H&E whole slide images from 1,094 previously untreated p16 positive OPSCC patients were acquired from six institutions for optimizing and validating MuNI.

RESULTS: MuNI was prognostic for disease-free (DFS), overall (OS), or distant metastasis-free (DMFS) survival in p16 positive 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, and T/N-categories in multivariable analyses. It was also prognostic for DFS, OS, and DMFS in OPSCC patients at stages I and III.

CONCLUSIONS: MuNI holds promise as a low-cost, tissue non-destructive, H&E stain based digital biomarker test for counseling, treatment, and surveillance of p16 positive OPSCC patients. These data support further confirmation of MuNI in prospective trials.

PubMed ID: 33651718

Article Size: 7.84 MB

Koyuncu CF, Frederick MJ, Thompson LDR, Corredor G, Khalighi S, Zhang Z, Song B, Lu C, Nag R, Sankar Viswanathan V, Gilkey M, Yang K, Koyfman SA, Chute DJ, Castro P, Lewis JS Jr, Madabhushi A, Sandulache VC.

Oral Oncol. 2023 Aug;143:106459. doi: 10.1016/j.oraloncology.2023.106459.

Objectives: Matching treatment intensity to tumor biology is critical to precision oncology for head and neck
squamous cell carcinoma (HNSCC) patients. We sought to identify biological features of tumor cell multinucleation,
previously shown by us to correlate with survival in oropharyngeal (OP) SCC using a machine
learning approach.

Materials and methods: Hematoxylin and eosin images from an institutional OPSCC cohort formed the training set
(DTr). TCGA HNSCC patients (oral cavity, oropharynx and larynx/hypopharynx) formed the validation set (DV ).
Deep learning models were trained in DTr to calculate a multinucleation index (MuNI) score. Gene set enrichment
analysis (GSEA) was then used to explore correlations between MuNI and tumor biology.

Results: MuNI correlated with overall survival. A multivariable nomogram that included MuNI, age, race, sex, T/
N stage, and smoking status yielded a C-index of 0.65, and MuNI was prognostic of overall survival (2.25,
1.07–4.71, 0.03), independent of the other variables. High MuNI scores correlated with depletion of effector
immunocyte subsets across all HNSCC sites independent of HPV and TP53 mutational status although the correlations
were strongest in wild-type TP53 tumors potentially due to aberrant mitotic events and activation of
DNA-repair mechanisms.

Conclusion: MuNI is associated with survival in HNSCC across subsites. This may be driven by an association
between high levels of multinucleation and a suppressive (potentially exhausted) tumor immune microenvironment.
Mechanistic studies examining the link between multinucleation and tumor immunity will be required
to characterize biological drivers of multinucleation and their impact on treatment response and outcomes.

PubMed ID: 37307602

Article Size: 2.5 MB

Bhattasali O, Ryoo JJ, Thompson LDR, Abdalla IA, Chen J, Iganej S.

Oral Oncol. 2019 Aug;95:74-78. doi: 10.1016/j.oraloncology.2019.06.007. Epub 2019 Jun 11.

OBJECTIVES: Although human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is typically associated with a good prognosis, patients with T4 disease experience relatively high rates of treatment failure. Our aim was to identify predictors of relapse among patients with clinical T4 disease.

MATERIAL & METHODS: A retrospective review was conducted of 93 consecutive patients who underwent definitive concurrent chemoradiation for HPV-associated OPSCC with clinical T4 disease from July 2006 to December 2015. Three-year outcomes, including locoregional recurrence (LRR), distant metastasis (DM), overall survival (OS), and cancer-specific survival (CSS), were examined and reported from the date of treatment completion. Multivariable analysis using a Cox proportional hazards model was performed to test associations between outcome and patient and disease characteristics as well as chemotherapy regimen (high-dose cisplatin (HDC) vs. other).

RESULTS: Median follow-up for surviving patients was 50 months (range 18-133). For all-comers, 3-year rates of LRR, DM, OS, and CSS were 15%, 19%, 79%, and 86%, respectively. On multivariable analysis, the only factor prognostic for patient outcomes was the chemotherapy regimen. For patients who received HDC vs. an alternative regimen, 3-year LRR, DM, OS, and CSS, were 9% vs. 20% (p = 0.09), 10% vs. 28% (p = 0.04), 89% vs. 67% (p = 0.04), and 96% vs. 77% (p = 0.02), respectively.

CONCLUSION: In patients with HPV-associated OPSCC bearing clinical T4 disease, receipt of a concurrent systemic agent other than HDC resulted in increased treatment failure and inferior survival. This analysis suggests that HDC should remain the preferred concurrent regimen for these patients.

PubMed ID: 31345397

Article Size: <1 MB

Bhattasali O, Thompson LDR, Schumacher AJ, Iganej S.

Head Neck. 2019 Feb;41(2):398-402. doi: 10.1002/hed.25504.

BACKGROUND: The updated AJCC Cancer Staging Manual groups all p16-positive oropharyngeal squamous cell carcinoma (OPSCC) with unilateral nodal involvement within 6 cm into the new clinical N1 classification, consolidating a heterogeneous group of disease with varying radiographic findings.

METHODS: A central radiological review was conducted identifying 233 patients with stage I node-positive (cT1-2N1) disease who underwent definitive concurrent chemoradiation. Factors evaluated included lymph node size, low-neck lymphadenopathy, retropharyngeal lymphadenopathy, overt radiographic extracapsular extension, and matted lymphadenopathy.

RESULTS: On multivariate analysis adjusted for age, smoking history, and chemotherapy regimen, low-neck lymphadenopathy (hazard ratio (HR) = 6.55; P < .001) and retropharyngeal lymphadenopathy (HR = 3.36; P = .009) predicted for inferior progression-free survival (PFS). low-neck lymphadenopathy (HR = 6.38; P = .001) and retropharyngeal lymphadenopathy (HR = 3.32; P = .02) also predicted for inferior overall survival (OS). All other radiographic characteristics showed no prognostic impact for PFS or OS.

CONCLUSIONS: This analysis suggests that caution should be advised against de-intensification efforts among patients with stage I node-positive p16-positive OPSCC with low-neck lymphadenopathy or retropharyngeal lymphadenopathy.

PubMed ID: 30552839

Article Size: <1 MB

 

Thompson LD, Heffner DK.

Cancer. 1998 Mar 1;82(5):944-56.

BACKGROUND: Predominantly cystic squamous cell carcinomas in the neck often present without a clinically apparent primary and therefore are frequently considered to be of branchial cleft origin. It is the authors’ hypothesis that the anatomic site of the primary carcinoma that produced the neck metastasis can often be predicted on the basis of the histologic features.

METHODS: Cases of cystic squamous cell carcinoma in the neck diagnosed between 1971 and 1991 were retrieved from the Otorhinolaryngic Pathology Registry of the Armed Forces Institute of Pathology. Histologic features were reviewed and patient follow-up was obtained and analyzed.

RESULTS: In cases wherein the primary site was discovered subsequently, 64% of the primaries were in the lingual or faucial tonsil. An additional 8% of cases were in nasopharyngeal tonsillar tissue. The cases that did not originate in Waldeyer’s tonsillar ring generally differed in histologic appearance from the tonsillar cases. The tonsillar primaries were discovered within an average of 12.4 months, but many were not discovered for years (up to 11 years). Most were small, indicating a slower growth of the primary than is usually expected for squamous cell carcinoma. Patients with such carcinomas had a much better prognosis than patients with metastatic squamous cell carcinomas of other upper airway mucosal sites.

CONCLUSIONS: In most cases of prominently cystic squamous cell carcinomas in the upper neck, the origin of the primary site will be in faucial or lingual tonsillar crypt epithelium. Knowledge of the probable site of origin allows for more tailored therapy in which the patients can be treated relatively conservatively with surgical excision and subsequent field-limited radiation therapy only, with 77% survival at 5 years. None of the cases reviewed in this study was a branchiogenic carcinoma.

PubMed ID: 9486586

Article Size: 2 MB

 

Bhattasali O, Torres FA, Kang HK, Thompson LDR, Abdalla IA, McNicoll MP, Lin A, Ryoo JJ, Chen J, Iganej S.

Oral Oncol. 2021 Mar;114:105147. doi: 10.1016/j.oraloncology.2020.105147. Epub 2021 Jan 16.

FIRST PARAGRAPH: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is established as a disease with generally favorable outcomes, particularly when contrasted to other head and neck squamous cell carcinomas which are commonly associated with heavy alcohol and tobacco use [1,2]. Prior cancer staging systems did not accurately prognosticate outcomes for HPV-associated OPSCC. Consequently, the American Joint Committee on Cancer (AJCC) 8th edition staging system reclassified HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) as its own entity and adapted the risk-stratification system proposed by the ICON-S group for this cohort of patients [3].

PubMed ID: 33460883

Article Size: 1 MB

Iganej S, Beard BW, Chen J, Buchschacher GL Jr, Abdalla IA, Thompson LDR, Bhattasali O.

Oral Oncol. 2019 Aug 2;97:18-22. doi: 10.1016/j.oraloncology.2019.07.016. [Epub ahead of print]

OBJECTIVE: We compared high-dose cisplatin (HDC) vs. triweekly carboplatin (TC)-based chemoradiation in patients with HPV-associated oropharyngeal squamous cell carcinoma (OPSCC).

MATERIALS AND METHODS: A retrospective review was conducted from 2006 to 2015 of 421 patients with locally advanced p16-positive OPSCC receiving definitive radiotherapy concurrent with 3 cycles of HDC (100 mg/m2, n = 230) or TC (AUC = 5, n = 191). Three-year locoregional recurrence (LRR), distant metastasis (DM), overall recurrence rate (ORR), overall survival (OS), and cause-specific survival (CSS) are reported. HDC and TC were compared accounting for age, sex, comorbidity index score, smoking history, T stage, and N stage.

RESULTS: For all-comers, no difference was observed between HDC and TC for any outcome except for ORR which was lower in patients receiving HDC (12% vs. 17%, p = 0.03). On stage-based analysis, no difference was observed between agents for any outcome for stage I or II disease. However, patients with stage III disease receiving HDC had lower rates of LRR (9% vs. 21%, p = 0.03), DM (7% vs. 28%, p = 0.006), and ORR (14% vs. 40%, p = 0.002), and superior OS (89% vs. 78%, p = 0.04) and CSS (95% vs. 80%, p = 0.02). Patients receiving HDC experienced higher rates of grade 3 leukopenia (25% vs. 11%, p < 0.001), weight loss ≥20% from baseline (21% vs. 8%, p < 0.001), and gastrostomy-tube placements (66% vs. 27%, p < 0.001).

CONCLUSION: TC demonstrated comparable outcomes to HDC for stage I or II HPV-associated OPSCC but was inferior to HDC for stage III disease. TC was associated with less toxicity and may be a potential de-intensification agent for early-stage disease.

PubMed ID: 31421466

Article Size: <1 MB

Bhattasali O, Thompson LDR, Abdalla IA, Chen J, Iganej S.

Rep Pract Oncol Radiother 23 (2018) 451-457.

Aim: To perform a comparison of Cisplatin vs. Cetuximab in p16-positive oropharyngealsquamous cell carcinoma (OPSCC) in the context of the revised HPV-based staging.

Background: Previous reports comparing these agents in head and neck cancer haveincluded heterogenous disease and p16-status.

Materials and methods: A retrospective review was conducted from 2006 to 2016 ofpatients with p16-positive OPSCC who underwent definitive radiotherapy concurrent witheither triweekly Cisplatin (n = 251) or Cetuximab (n = 40). AJCC 8th Edition staging wasadapted.

Results: Median follow-up for surviving patients was 40 months. On multivariate analysisfor all-comers, comparing Cisplatin and Cetuximab, 3-year locoregional recurrence (LRR):6% vs. 16% (p = 0.07), 3-year distant metastasis (DM): 8% vs. 21% (p = 0.04), 3-year overallrecurrence rate (ORR): 11% vs. 29% (p = 0.01), and 3-year cause-specific survival (CSS): 94%vs. 79% (p = 0.06), respectively. On stage-based subgroup analysis, for stage I II disease, 3-year LRR: 5% vs. 10% (p = 0.51), 3-year DM: 7% vs. 16% (p = 0.32), 3-year ORR: 10% vs. 23%(p = 0.15), and 3-year CSS: 95% vs. 82% (p = 0.38). For stage III disease, 3-year LRR: 10% vs. 40%(p = 0.07), 3-year DM: 9% vs. 43% (p = 0.07), 3-year ORR: 15% vs. 55% (p = 0.04), and 3-year CSS:94% vs. 57% (p = 0.048).

Conclusions: When given concurrently with radiotherapy, Cetuximab and triweekly Cisplatin demonstrated comparable efficacy for AJCC 8th Edition stage I–II p16-positive OPSCC. However, Cetuximab appeared to be associated with higher rates of treatment failure and cancer-related deaths in stage III disease. Upon availability of the RTOG 1016 trial results, analysis based on the revised HPV-based staging should be performed to confirm these
findings.

PubMed ID: n/a

Article Size: <1 MB

 

Koyuncu CF, Nag R, Lu C, Corredor G, Viswanathan VS, Sandulache VC, Fu P, Yang K, Pan Q, Zhang Z, Xu J, Chute DJ, Thorstad WL, Faraji F, Bishop JA, Mehrad M, Castro PD, Sikora AG, Thompson LDR, Chernock RD, Lang Kuhs KA, Wasman JK, Luo JR, Adelstein DJ, Koyfman SA, Lewis JS Jr, Madabhushi A.

Cancer 2022 Nov 1;128(21):3831-3842. doi: 10.1002/cncr.34446. Epub 2022 Sep 6.

BACKGROUND: Understanding biological differences between different racial groups of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) patients, who have differences in terms of incidence, survival, and tumor morphology, can facilitate accurate prognostic biomarkers, which can help develop personalized treatment strategies.

METHODS: This study evaluated whether there were morphologic differences between HPV-associated tumors from Black and White patients in terms of multinucleation index (MuNI), an image analysis-derived metric that measures density of multinucleated tumor cells within epithelial regions on hematoxylin–eosin images and previously has been prognostic in HPV-associated OPSCC patients. In this study, the authors specifically evaluated whether the same MuNI cutoff that was prognostic of overall survival (OS) and disease-free survival in their previous study, TTR, is valid for Black and White patients, separately. We also evaluated population-specific cutoffs, TB for Blacks and TW for Whites, for risk stratification.

RESULTS: MuNI was statistically significantly different between Black (mean, 3.88e–4; median, 3.67e–04) and White patients (mean, 3.36e–04; median, 2.99e–04), with p = .0078. Using TTR, MuNI was prognostic of OS in the entire population with hazard ratio (HR) of 1.71 (p = .002; 95% confidence interval [CI], 1.21–2.43) and in White patients with HR of 1.72 (p = .005; 95% CI, 1.18–2.51). Population-specific cutoff, TW, yielded improved HR of 1.77 (p = .003; 95% CI, 1.21–2.58) for White patients, whereas TB did not improve risk-stratification in Black patients with HR of 0.6 (p = .3; HR, 0.6; 95% CI, 0.2–1.80).

CONCLUSIONS: Histological difference between White and Black patient tumors in terms of multinucleated tumor cells suggests the need for considering population-specific prognostic biomarkers for personalized risk stratification strategies for HPV-associated OPSCC patients.

PubMed ID: 36066461

Article Size: 6 MB

Palsgrove DN, Rooper LM, Stevens TM, Shin C, Damm DD, Gagan J, Bridge JA, Thompson LDR, Koduru PR, Bishop JA.

Head Neck Pathol. 2022 Dec;16(4):1146-1156.

BACKGROUND: GLI1 is a transcription factor protein that has recently gained recognition in a morphologically distinct group of epithelioid soft tissue tumors characterized by GLI1 fusions or amplifications. The head and neck region, particularly the tongue, is a common location for GLI1-altered tumors. DDIT3 break apart fluorescence in situ hybridization (FISH), commonly used to identify translocations in myxoid/round cell liposarcoma, has been used as a surrogate test to detect both fusions and amplifications of the 12q13.3 region encompassing DDIT3 and GLI1 gene loci.

METHODS: We herein report 5 cases of GLI1-altered soft tissue tumors. Three arose in the oropharynx (base of tongue/vallecula, tonsil) and two arose in the tongue. Given the frequent oropharyngeal location and epithelioid morphology, p16 immunohistochemistry was performed on cases with available material. Commercially available DDIT3 break apart FISH, custom GLI1 specific FISH, and RNA sequencing were performed on select cases.

RESULTS: Two cases showed amplification using DDIT3 FISH which was confirmed using GLI1 specific FISH. The remaining cases harbored ACTB::GLI1, one of which showed rearrangement of the 12q13.3 region by DDIT3 FISH with absence of amplification by GLI1 specific FISH. STAT6 immunoexpression was positive in the GLI1-amplified cases and negative in the GLI1-rearranged cases while MDM2 expression was positive in the 4 cases tested. CDK4 expression was strong and diffuse in the GLI1-amplified cases. p16 immunohistochemistry showed strong nuclear and cytoplasmic staining in 50-70% of tumor cells in all four tested cases.

CONCLUSIONS: Here we show that GLI1-altered soft tissue tumors are frequently positive for p16 and can occur in tonsillar regions of the oropharynx. As such, positive p16 immunohistochemistry alone cannot be used as evidence for the diagnosis of HPV-related squamous cell carcinoma as strong and diffuse p16 expression may also occur in GLI1-altered soft tissue tumors. Commercially available DDIT3 break apart FISH, which is readily available in many cytogenetic laboratories, may be useful as a sensitive surrogate test for GLI1 fusions and amplifications.

PubMed ID: 35933574

Article Size: 4.8 MB

Randall DA, Martin PJ, Thompson LD.

Laryngoscope. 2007 Sep;117(9):1600-4

OBJECTIVE: To determine whether the current practice and incurred cost of histologic examination of tonsillectomy and adenoidectomy specimens is warranted.

STUDY DESIGN: Review article based on medical literature.

SUBJECTS AND METHODS: A retrospective PubMed review of all pertinent literature regarding tonsillectomy, adenoidectomy, and related surgical pathology was conducted. References of the articles obtained were reviewed for additional sources.

RESULTS: Twenty studies report 54,901 patients and found 54 malignancies (0.087% prevalence). Of these, 48 (88% of the patients) had suspicious features such as tonsillar asymmetry, cervical lymphadenopathy, or abnormal tonsil appearance, preoperatively. The remaining six patients without any suspicious features (better representing true occult malignancy) were 0.011% of the total cases.

CONCLUSION: Submission of tonsillectomy, adenoidectomy, or both specimens is warranted only when patients demonstrate findings associated with malignancy: tonsillar asymmetry, history of cancer, neck mass, tonsil firmness or lesion, weight loss, and constitutional symptoms.

PubMed ID: 17762791

Article Size: <1 MB

 

Kardon DE, Wenig BM, Heffner DK, Thompson LD.

Mod Pathol. 2000 Oct;13(10):1128-33.

BACKGROUND: Lymphangiomatous polyps are uncommon benign tumors of the tonsils.

METHODS: Twenty-six cases of lymphangiomatous polyps diagnosed between 1980 and 1999 were retrieved from the files of the Otorhinolaryngic-Head and Neck Tumor Registry of the Armed Forces Institute of Pathology. Hematoxylin and eosin-stained slides were reviewed to characterize the histologic features of these tumors. Immunohistochemical stains were performed on 15 cases. Clinical follow-up data were obtained.

RESULTS: The patients included 13 males and 13 females, ages 3 to 63 years (mean, 25.2 years). Patients experienced dysphagia, sore throat, and the sensation of a mass in the throat. Symptoms were present from a few weeks to years. The tonsillar masses were unilateral in all cases. Clinically, the lesions were frequently mistaken for a neoplasm (n = 18 patients). Grossly, all of the lesions were polypoid and measured 0.5 to 3.8 cm (mean, 1.6 cm). Histologically, the polyps were covered by squamous epithelium showing variable epithelial hyperplasia, dyskeratosis, and lymphocytic epitheliotropism. The masses showed a characteristic submucosal proliferation of small to medium-sized, endothelial-lined, lymph-vascular channels lacking features of malignancy. Collagen, smooth muscle, and adipose tissue were present in the stroma. Intravascular proteinaceous fluid and lymphocytes were noted. Immunohistochemical findings confirmed the endothelial origin of the vascular proliferation and a mixed lymphoid population. The differential diagnosis included fibroepithelial polyp, lymphangioma, juvenile angiofibroma, and squamous papilloma. In all patients with follow-up, complete surgical excision was curative (mean follow-up, 5.4 years; range, 1 mo to 14 years).

CONCLUSIONS: We detail the clinical and pathologic features of tonsillar lymphangiomatous polyps. These tumors are uncommon and may clinically be mistaken for a malignant neoplasm. The characteristic histologic features should allow for its correct diagnosis and differentiation from similar appearing tonsillar lesions.

PubMed ID: 11048808

Article Size: 2.5 MB

 

Frankel SS, Wenig BM, Burke AP, Mannan P, Thompson LD, Abbondanzo SL, Nelson AM, Pope M, Steinman RM.

Science. 1996 Apr 5;272(5258):115-7. — Comment in: Science. 1996 Nov 15;274(5290):1067-8.

Human immunodeficiency virus-type 1 (HIV-1) replicates actively in infected individuals, yet cells with intracellular depots of viral protein are observed only infrequently. Many cells expressing the HIV-1 Gag protein were detected at the surface of the nasopharyngeal tonsil or adenoid. This infected mucosal surface contained T cells and dendritic cells, two cell types that together support HIV-1 replication in culture. The infected cells were multinucleated syncytia and expressed the S100 and p55 dendritic cell markers. Eleven of the 13 specimens analyzed were from donors who did not have symptoms of acquired immunodeficiency syndrome (AIDS). The interaction of dendritic cells and T cells in mucosa may support HIV-1 replication, even in subclinical stages of infection.

PubMed ID: 8600520

Article Size: 2.5 MB

 

Wenig BM, Thompson LD, Frankel SS, Burke AP, Abbondanzo SL, Sesterhenn I, Heffner DK.

Am J Surg Pathol. 1996 May;20(5):572-87.

We report 12 cases in which the histomorphologic changes of the nasopharyngeal tonsils (adenoids) or palatine tonsils suggest infection with the human immunodeficiency virus (HIV). The patients included 10 men and two women, aged 20 to 42 years (median, 33 years). The clinical presentation included airway obstruction, pharyngitis, fever, and a tonsillar or adenoidal mass lesion. Histologic evaluation of the excised adenoids or tonsils in 10 of the cases demonstrated a spectrum of changes including florid follicular hyperplasia, follicle lysis, attenuated mantle zone, and the presence of multinucleated giant cells (MGC). The latter characteristically localized adjacent to the surface or tonsillar crypt epithelium. Two of the 12 cases showed marked lymphoid depletion with absent germinal centers, plasmacytosis, and stromal vascular proliferation. Immunohistochemical evaluation for HIV p24 core protein showed reactivity in 10 of 12 cases localized to follicular dendritic cell network (FDC), the MGC, scattered interfollicular lymphoid cells, and cells identified within the surface or crypt epithelium. Localization of viral RNA by in situ hybridization paralleled the HIV p24 immunohistochemical findings. Additional significant findings included the presence of both CD-68 and S-100 protein in the MGC and the presence of S-100 protein in dendritic cells. Other than HIV, no microorganisms were identified. At the time of presentation, eight patients were not known to be a risk for HIV infection, nor were they known to be HIV infected or suffering from AIDS. In these patients, HIV infection was suspected on the basis of the histologic changes seen in the resected tonsillar and adenoidal tissue. Serologic evaluation (by enzyme-linked immunosorbent assay), confirmed the presence of HIV infection. Our findings suggest the possibility of HIV dissemination through the upper aero-digestive tract mucosa via target cells, such as intraepithelial dendritic cells, submucosal macrophages, and T-lymphocytes. Subsequent presentation of viral antigens to the tonsillar and adenoidal lymphoid tissues results in enlargement of these structures that clinically may simulate a neoplastic proliferation but causes histomorphologic changes that are highly suspicious for HIV infection even in asymptomatic HIV-positive patients.

PubMed ID: 8619422

Article Size: 4 MB

 

Woolgar JA, Triantafyllou A, Lewis JS Jr, Hunt J, Williams MD, Takes RP, Thompson LD, Slootweg PJ, Devaney KO, Ferlito A.

Eur Arch Otorhinolaryngol. 2013 May;270(5):1581-92.

The superior prognostic value offered by routine histopathological staging of neck dissections, as compared to clinical staging using palpation and modern imaging techniques, is well established in the literature concerning the management of squamous cell carcinoma of the head and neck. In this review, we discuss the definitions and criteria used in standardised routine histopathological reporting and explore additional potential nodal prognostic features. In addition, we critically appraise the value of immunohistochemistry, histochemistry, molecular and other non-morphological techniques and suggest tumour and host features that merit further investigations.

PubMed ID: 22983222

Article Size: 1 MB

 

Payne T, Di Palma S, Walker D, Dakin J, Thompson LDR.

Head Neck Pathol. 2021 Sep;15(3):1047-1053. doi: 10.1007/s12105-020-01245-w.

Extragonadal non-gestational choriocarcinoma is a rare but well-described phenomenon occurring in patients with midline germ cell tumors. Choriocarcinoma (ChC) is an aggressive neoplasm usually developing in women as a rare complication of pregnancy. In male patients ChC occurs in the testes, usually as a component of mixed germ cell tumors. Very few patients develop extragonadal choriocarcinoma with the tumor occurring in midline locations, such as the mediastinum, retroperitoneum, and central nervous system (mostly pineal gland). Non-midline choriocarcinoma can occur in the lung, gastrointestinal tract, and breast, sometimes blended with another primary malignancy. A midline choriocarcinoma manifesting as a head and neck malignancy is exceptional. During an evaluation of multiple enlarged cervical lymph nodes suspected to be lymphoma in a 72-year-old man, a core biopsy was taken from one of the left neck lymph nodes which histologically showed a necrotic malignancy with strong diffuse pancytokeratin staining. After an initial interpretation of metastatic carcinoma, further samples were taken from both tonsils and from a right level 5 neck lymph node. Histologically, all samples contained the same tumor, showing profound pleomorphism and multinucleated syncytial-type giant cells. A panel of immunohistochemistry studies were performed, including β-human chorionic gonadotropin, with positive findings leading to a diagnosis of extragonadal non-gestational choriocarcinoma.

PubMed ID: 33128732

Article Size: 2 MB

Heffner DK, Thompson LD, Schall DG, Anderson V.

Ann Otol Rhinol Laryngol. 1996 Oct;105(10):819-24.

The purpose of this study is to clarify the origin and nature of so-called hairy polyps or dermoids of the pharynx, which are often thought to be a variant of pharyngeal teratoma. For this purpose, a case is reported of a dermoid polyp involving the middle ear of an infant, the features of multiple examples of pharyngeal dermoid polyps and teratomas received for consultation by the Armed Forces Institute of Pathology are examined, and selected pertinent reports from the literature are reviewed. All three means are used to support the conclusion that these lesions are choristomatous developmental anomalies arising from the first branchial cleft area and that they essentially represent heterotopic accessory ‘ears’ (auricles) without the growth potential of a teratoma.

PubMed ID: 8865778

Article Size: <1 MB

 

Thompson LD.

Ear Nose Throat J. 2005 May;84(5):272-3.

FIRST PARAGRAPH: Metastatic disease to the lymph nodes of the neck is an important clinical and pathologic consideration. When there is no known primary, the pathologist and radiologist must provide additional input to the clinician during the work-up. This installment of PATHOLOGY CLINIC focuses on cervical cystic squamous cell carcinoma (cSCC), which is commonly misdiagnosed as squamous cell carcinoma arising in a branchiogenic cyst or as a branchiogenic carcinoma.

PubMed ID: 15971745

Article Size: <1 MB

Kardon DE, Thompson LD.

Laryngoscope. 2000 Mar;110(3 Pt 1):476-81.

OBJECTIVES: Tonsils are uncommonly affected by granulomatous inflammation, often with an obscure cause. This study attempts to elucidate the nature of tonsillar granulomatous inflammation.

DESIGN: Retrospective clinicopathologic review.

METHODS: Twenty-two cases of tonsillar granulomas diagnosed between 1940 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. H&E slides and a series of histochemical stains were reviewed, and patient follow-up was obtained.

RESULTS: There were 11 males and 11 females, aged 7 to 64 years (mean, 29.9 y). Most of the cases presented bilaterally (n = 19) with sore throat, dysphagia, and/or nasal obstruction. The clinical differential included chronic tonsillitis, tuberculosis, nonspecific infection, sarcoidosis, and a neoplasm. Histologically, the granulomas were focal and scattered, or diffuse, identified in the interfollicular zones (n = 16) and/or the germinal centers (n = 13), and occasionally associated with necrosis (n = 6). Based on histochemical and clinical follow-up information, the etiology of the granulomas included sarcoidosis (n = 8), tuberculosis (n = 3), Hodgkin’s lymphoma (n = 2), toxoplasmosis (n = 1), squamous cell carcinoma (n = 1), and no specific known cause (n = 7). Twelve patients were either alive at last follow-up or had died with no evidence of disease (mean, 12.4 y), and 9 were either alive at last follow-up or had died with disease (mean, 24.9 y). One patient was alive with unknown disease status (lost to follow-up after 13.3 y).

CONCLUSIONS: Although a cause for tonsillar granulomas is frequently identified, a number may not develop an identifiable etiology, with the granulomas probably representing an exaggerated immune response to chronic tonsillitis. However, a careful work-up must be conducted to exclude specific causes and avoid clinical mismanagement.

PubMed ID: 10718441

Article Size: 1 MB

 

Borhan WM, Dababo MA, Thompson LD, Saleem M, Pashley N.

Head Neck Pathol. 2015 Mar;9(1):119-22.

The finding of herpetic tonsillitis is rare. Tonsillectomies are usually done for children with recurrent chronic tonsillitis, while viral throat infections are generally self-limiting. We present two cases: A 5 yearold girl, with atypical hemolytic anemia managed with Eculizumab, who presented with a pharyngeal infection and tonsillar enlargement that did not respond to intravenous antibiotics or antifungal therapies; and a 30 yearold man who presented with upper airway obstruction and fever; bilateral tonsillectomies were performed. Histopathological examination showed a necrotizing tonsillitis with numerous ground-glass intranuclear inclusions, characteristic of herpes viral infection, further confirmed by Herpes simplex virus in situ hybridization. Both patients were managed by intravenous Acyclovir, with dramatic improvement.

PubMed ID: 24338612

Article Size: <1 MB

 

Nelson BL, Thompson LD.

Ear Nose Throat J. 2003 Mar;82(3):178.

FIRST PARAGRAPH: Tangier disease is a rare autosomal-recessive inherited disorder that is caused by a defect in chromosome 9q31. It is characterized by a severe deficiency or absence of high-density lipoproteins in plasma. A defect in cellular cholesterol removal results in the massive, abnormal accumulation of cholesterol esters in macrophages in many tissues. Although this accumulation is most conspicuous in the tonsils, progressive accretion of these esters also occurs in nerves (neuropathy) and vessels (atherosclerosis). The pathognomonic finding is a low plasma cholesterol concentration accompanied by normal or elevated triglyceride levels and large, lobulated, hyperplastic, bright orange-yellow tonsils and adenoid tissue. Affected families have been identified on Tangier Island, Va., in Chesapeake Bay as well as in Missouri, Kentucky, and Europe.

PubMed ID: 12696235

Article Size: <1 MB