Lester D. R. Thompson, MD – Page 3 – Lester D. R. Thompson, MD

Odontoma.

30DecemberLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Article Size: <1 MB

Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features.

30DecemberLester D. R. Thompson, MDEndocrine, Thyroid

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):533S-535S. doi: 10.1177/0145561319890162.

FIRST PARAGRAPH: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently recognized indolent neoplasm separated from invasive follicular variant of papillary thyroid carcinoma (FVPTC). NIFTP is a noninvasive, partially to completely encapsulated thyroid follicular neoplasm arranged in almost exclusively follicular architecture, showing papillary carcinoma-like nuclear features in an adequately sampled tumor. In order to qualify for placement in this category, several inclusion and exclusion criteria must be met. Importantly, there can be no invasion at the tumor periphery (ie, usually the capsule) that has been completely sampled for histologic review. There cannot be another recognized pattern of papillary carcinoma, and no more than 30% of the tumor should be solid, trabecular, or insular. There cannot be any tumor necrosis and no increased mitoses of _4 mitoses/2 mm2. Finally, there cannot be any true papillary structures.

PubMed ID: 31760798

Article Size: <1 MB

Inflammatory Myofibroblastic Tumor.

30DecemberLester D. R. Thompson, MDHead & Neck, Larynx

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):520S-521S. doi: 10.1177/0145561319890165.

FIRST PARAGRAPH: Inflammatory myofibroblastic tumor (IMT) is a distinctive, rarely metastasizing, (myo)fibroblastic neoplasm composed of spindle cells accompanied by an inflammatory infiltrate of plasma cells, lymphocytes, and/or eosinophils. Genetically, most IMTs harbor tyrosine kinase fusions, usually the ALK gene with an ever-expanding list of partner genes (TIMP3-ALK is most common), although these rearrangements are rare in adults. More common in abdominal soft tissue and lung sites, head and neck tumors comprise about 20% of all IMTs. Children and young adults are usually affected, with a slight female predominance. Symptoms are nonspecific and generally related to obstructive symptoms due to mass effect. Patients are generally managed surgically, although molecular-targeted therapy (eg, crizotinib) shows good response. While metastatic disease is exceptional, local recurrences are seen in about 25% of patients.

PubMed ID: 31760795

Article Size: <1 MB

IgG4-Related Sialadenitis.

30DecemberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):531S-532S. doi: 10.1177/0145561319890153.

FIRST PARAGRAPH: IgG4-related sialadenitis, formally Ku¨ttner tumor, is a chronic fibroinflammatory tumefactive salivary gland disorder characteristically showing dense lymphoplasmacytic infiltrate, storiform fibrosis, phlebitis, and increased IgG4-positive plasma cells, often with elevated serum IgG4 concentrations. This immune-mediated disorder often has systemic findings, including autoimmune pancreatitis, retroperitoneal fibrosis, cholangitis, lacrimal gland dacryoadenitis, Riedel thyroiditis, and other glands affected by a similar inflammatory fibroblastic disorder. The disorder is characterized by a prominent lymphoplasmacytic infiltrate and cytotoxic T-cell populations. In some submandibular cases, sialolithiasis may be a confounding factor.

PubMed ID: 31760789

Article Size: <1 MB

Desmoid-Type Fibromatosis.

30DecemberLester D. R. Thompson, MDHead & Neck, Neck

Thompson LDR.

Ear Nose Throat J. 2021 Sep;100(5_suppl):518S-519S. Doi: 10.1177/0145561319890151.

FIRST PARAGRAPH: Desmoid-type fibromatosis is a locally aggressive, nonmetastasizing, well-differentiated, unencapsulated monoclonal myofibroblastic proliferation with a tendency for local invasion and recurrence. The tumor is intermediate between a fibroma and fibrosarcoma. Without a well documented etiology, trauma, surgery, and mutations in the CTNNB1 gene have all been implicated.

PubMed ID: 31760797

Article Size: <1 MB

Primary Thyroid Gland Alveolar Soft Part Sarcoma

30NovemberLester D. R. Thompson, MDEndocrine, Thyroid

Whaley RD, Thompson LDR.

Head Neck Pathol. 2020 Sep;14(3):701-706. doi: 10.1007/s12105-019-01099-x. Epub 2019 Nov 28.

Alveolar soft part sarcoma (ASPS) is a rare soft tissue tumor of unknown histogenesis generally characterized by the der(17)t(X;17)(p11.2;q25) translocation which results in the ASPSCR1-TFE3 gene fusion. Primary ASPS of the thyroid gland has not yet been reported. During oncology follow-up for breast cancer, a pulmonary nodule and thyroid gland mass were identified in a 71-year-old Korean male. Thyroid ultrasound showed a 5.7 cm left thyroid gland mass. After several fine needle aspirations, a thyroid gland lobectomy was performed after documenting only non-caseating granulomatous inflammation in a biopsy of the lung nodule. A 7.6 cm bulging nodular thyroid gland mass was identified, showing significant destructive invasion. Alveolar nests of large polygonal, eosinophilic, granular neoplastic cells were separated by vascularized stroma. Colloid was absent. Tumor necrosis and increased mitoses were identified. The neoplastic cells were positive with TFE3 and CD68, but negative with pancytokeratin, thyroglobulin, TTF-1, napsin-A, calcitonin, PAX8, CAIX, S100 protein, HMB45, SMA, and desmin. FISH confirmed a TFE3 gene rearrangement. The differential includes several primary thyroid gland epithelial neoplasms, paraganglioma, PEComa, melanoma, crystal storage disease, and metastatic carcinomas, especially Xp11 translocation renal cell carcinoma. The patient has refused additional therapy, but is alive without tumor identified (primary or metastatic).

PubMed ID: 31782115

Article Size: 1.9 MB

NCOA4-RET and TRIM27-RET Are Characteristic Gene Fusions in Salivary Intraductal Carcinoma, Including Invasive and Metastatic Tumors: Is “Intraductal” Correct?

21NovemberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Skálová A, Ptáková N, Santana T, Agaimy A, Ihrler S, Uro-Coste E, Thompson LDR, Bishop JA, Baněčkova M, Rupp NJ, Morbini P, de Sanctis S, Schiavo-Lena M, Vanecek T, Michal M, Leivo I.

Am J Surg Pathol. 2019 Oct;43(10):1303-1313. doi: 10.1097/PAS.0000000000001301.

Intraductal carcinoma (IC) is the new WHO designation for tumors previously encompassed by “low-grade cribriform cystadenocarcinoma” and “low-grade salivary duct carcinoma.” The relationship of IC to salivary duct carcinoma (SDC) is controversial, even though they are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with histopathological features reminiscent of atypical ductal hyperplasia or ductal carcinoma in situ of the breast, showing diffuse S100 protein and mammaglobin positivity, while it is partially defined genetically. Recently, RET rearrangements including NCOA4-RET and TRIM27-RET have been described in IC. Here, we genetically characterize the largest cohort of IC to date (33 cases) including 8 cases with focal or widespread invasive growth and 1 case with lymph node metastasis. Thirty-three cases of IC were analyzed by next-generation sequencing (NGS) using the FusionPlex Solid Tumor kit (ArcherDX). Identified gene fusions were confirmed using fluorescence in situ hybridization break-apart and fusion probes and an reverse transcription polymerase chain reaction designed specifically for the detected breakpoints. Ten cases of SDC were analyzed for comparison using NGS panels that detect mutations and fusion transcripts. NGS analysis detected an NCOA4-RET fusion transcript in 11 cases of intercalated duct-type IC joining exon 7 or 8 of NCOA4 gene and exon 12 of the RET gene. Eight cases of IC had an invasive growth pattern, including one with widespread invasion and lymph node metastasis. Three invasive ICs harbored an NCOA4-RET fusion transcript, while 1 case was negative, and 2 cases were not analyzable. In addition, a novel TRIM27-RET fusion transcript between exon 3 of TRIM27 and exon 12 of RET was identified in 2 cases of IC with apocrine features, and one of them displayed invasive growth. Two IC cases with invasive growth harbored novel fusions TUT1-ETV5 and KIAA1217-RET, respectively. A total of 42.4% of the cases in this series of IC harbored fusions involving RET. Such fusion transcripts were not detected in any of the 10 SDC cases. We have confirmed NCOA4-RET as a predominant fusion in intercalated duct-type IC, including 3 cases with invasive growth pattern. A novel finding in our series was a case of widely invasive intercalated duct-type IC, with a single lymph node metastasis that revealed an NCOA4-RET fusion transcript. We also demonstrated that a subset of apocrine Ics harbored a TRIM27-RET gene fusion, including one case with invasive growth. In contrast, neither NCOA4-RET nor TRIM27-RET fusions were detected in any tested SDCs. Thus, the distinct molecular findings in IC and SDC support that the tumors are separate malignant salivary tumor entities. The presence of tumor-type-specific NCOA4-RET or TRIM27-RET translocations in a subset of widely invasive carcinomas with intercalated duct-like immunoprofiles suggests that a recharacterization of IC including its redesignation as “intercalated duct carcinoma, invasive or noninvasive” may be appropriate.

PubMed ID: 31162284

Article Size: <1 MB

Don’t stop the champions of research now: a brief history of head and neck pathology developments.

19NovemberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Thompson LDR, Lewis JS Jr, Skálová A, Bishop JA.

Hum Pathol. 2020 Jan;95:1-23. doi: 10.1016/j.humpath.2019.08.017. Epub 2019 Aug 23.

The field of Head and Neck Pathology was just developing 50years ago, but has certainly come a long way in a relatively short time. Thousands of developments in diagnostic criteria, tumor classification, malignancy staging, immunohistochemistry application and molecular testing have been made during this time, with an exponential increase in literature on the topics over the past few decades: There were 3506 articles published on head and neck topics in the decade between 1969 and 1978 (PubMed source), with a staggering 89266 manuscripts published in the most recent decade. It is daunting and impossible to narrow the more than 162000 publications in this field and suggest only a few topics of significance. However, the breakthru in this anatomic discipline has been achieved in three major sites: oropharyngeal carcinoma, salivary gland neoplasms, and sinonasal tract tumors. This review will highlight selected topics in these anatomic sites in which the most profound changes in diagnosis have occurred, focusing on the information that helps to guide daily routine practice of surgical pathology.

PubMed ID: 31449826

Article Size: 9.5 MB

Tongue Schwannoma: A Clinicopathologic Study of 19 Cases.

19NovemberLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Oropharyngeal Squamous Cell Carcinoma in 390 Patients: Analysis of Clinical and Histological Criteria Which Significantly Impact Outcome

19NovemberLester D. R. Thompson, MDHead & Neck, 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

Sclerosing Polycystic “Adenosis” of Salivary Glands: A Neoplasm Characterized by PI3K Pathway Alterations More Correctly Named Sclerosing Polycystic Adenoma.

18OctoberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Bishop JA, Gagan J, Baumhoer D, McLean-Holden AL, Oliai BR, Couce M, Thompson LDR.

Head Neck Pathol. 2020 Sep;14(3):630-636. doi: 10.1007/s12105-019-01088-0. Epub 2019 Oct 11.

Sclerosing polycystic adenosis (SPA) is a rare benign salivary gland lesion that usually arises from the parotid gland. SPA was originally interpreted to be a non-neoplastic alteration analogous to fibrocystic changes of the breast, but now there is uncertainty about whether it may represent a neoplasm. SPA often contains intraductal proliferations with an appearance similar to ductal neoplasia of the breast, and one study reported X-chromosome inactivation using polymorphisms of the human androgen receptor (Skalova et al., in AJSP 30:939-944, 2006). We investigated the genetics of SPA through targeted next generation sequencing (NGS). Four cases of SPA were retrieved from the authors’ consultation files. A custom, targeted NGS panel including 1425 cancer-related genes was performed on all cases, followed by immunohistochemistry for PTEN. All four cases developed in females, ranging from 40 to 69 years (mean 52.5 years), affecting the parotid (n = 3) and submandibular glands (n = 1). All cases exhibited characteristic histologic features of SPA: well-circumscribed lesions with fibrosis and an admixture of ducts, myoepithelial cells and acinar cells, the latter containing brightly eosinophilic intracytoplasmic granules. Two cases had intraductal apocrine epithelial proliferations. By targeted NGS, loss-of-function mutations in PTEN were revealed in all 4 cases. In addition, 2 of 4 cases harbored PIK3CA mutations and 2 of 4 possessed PIK3R1 alterations; one case lacked both PIK3CA and PIK3R1 mutations. PTEN expression by immunohistochemistry was lost in the ductal and acinar elements but not the myoepithelial cells in all cases. SPA is characterized by genetic alterations in the PI3K pathway, with PTEN mutations seen most frequently. This molecular profile is similar to salivary duct carcinoma and the apocrine variant of intraductal carcinoma (i.e., salivary duct carcinoma-in situ). PI3K pathway alterations were found in cases both with and without intraductal apocrine proliferations, and PTEN immunohistochemistry suggested that the ductal and acinar cells, but not myoepithelial cells, were affected. Taken together, these findings strongly support that SPA is a neoplasm, more correctly named “sclerosing polycystic adenoma.” The salivary duct carcinoma-like genetic alterations, coupled with the fact that the surrounding myoepithelial cells appear to be non-neoplastic, suggest a close relationship between SPA and apocrine intraductal carcinoma.

PubMed ID: 31605313

Article Size: 1.9 MB

Triweekly carboplatin as a potential de-intensification agent in concurrent chemoradiation for early-stage HPV-associated oropharyngeal cancer.

4SeptemberLester D. R. Thompson, MDHead & Neck, Oropharynx

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

Impact of chemotherapy regimen on treatment outcomes in patients with HPV-associated oropharyngeal cancer with T4 disease treated with definitive concurrent chemoradiation.

4SeptemberLester D. R. Thompson, MDHead & Neck, Oropharynx

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

HPV-Related Multiphenotypic Sinonasal Carcinoma.

4SeptemberLester D. R. Thompson, MDHead & Neck, Sinonasal Tract

Thompson LDR.

Ear Nose Throat J. 2020 Feb;99(2):94-95. doi: 10.1177/0145561319871711.

FIRST PARAGRAPH: Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (originally called HPV-related carcinoma with adenoid cystic-like features) is a recently recognized variant of sinonasal carcinoma showing histologic features of surface dysplasia and salivary gland carcinoma (adenoid cystic carcinoma specifically) and showing a strong association with HPV, especially HPV 33. Women are affected slightly more often than men, with a mean age at presentation in the sixth decade, frequently with high T-stage disease. Tumors involve the nasal cavity and paranasal sinuses, often with extension into adjacent structures. Even though the tumors are often large and destructive sinonasal tract tumors, they tend to exhibit a relatively indolent behavior, although local recurrence is frequent, but distant metastasis and death from disease are very uncommon. As such, this tumor should be distinguished from histologic mimics as there is a better prognosis.

PubMed ID: 31476886

Article Size: <1 MB

ImmunoQuery Demonstration

4AugustLester D. R. Thompson, MDThyroid

TIP: For sharpest focus, you may need to change YouTube’s default quality settings from Auto to 1080p60. Once you start the video, click the Settings cog icon near the lower right corner of video frame, select Quality and change Auto to 1080p. You should also click the Full Screen icon at the far right.

How to use Elsevier’s ExpertPath

21JulyLester D. R. Thompson, MDThyroid

TIP: For sharpest focus, you may need to change YouTube’s default quality settings from Auto to 1080p60. Once you start the video, click the Settings cog icon near the lower right corner of video frame, select Quality and change Auto to 1080p. You should also click the Full Screen icon at the far right.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Update and Diagnostic Considerations—a Review

16JulyLester D. R. Thompson, MDEndocrine, Thyroid

Rossi ED, Faquin WC, Baloch Z, Fadda G, Thompson LDR, Larocca LM, Pantanowitz L.

Endocr Pathol. 2019 Jun;30(2):155-162. doi: 10.1007/s12022-019-9574-7.

Advances in our understanding of thyroid lesions, especially those entities with an indolent behavior, has led clinicians to question the most appropriate surgical management of such thyroid nodules. Several studies have shown that the non-invasive encapsulated follicular variant of papillary thyroid carcinomas (NI-EFVPC) exhibits poor histopathologic diagnostic reproducibility and have been over-treated as conventional thyroid cancer. In 2015, an international thyroid working group re-evaluated NI-EFVPC and its diagnostic criteria. The new terminology of Bnoninvasive follicular thyroid neoplasm with papillary-like nuclear features^ (NIFTP) was accordingly introduced to replace NI-EFVPC. The literature has emphasized that NIFTPs are biologically similar to follicular adenomas lacking lymph node metastases and/or recurrence. While the definition of NIFTP is based on specific morphological parameters, recent studies have questioned whether the criterion allowing less than 1% of true papillae should be revised to a total absence of papillae. The motivation for this revision is the rare finding, in some studies, of lymph nodes with metastatic NIFTP. This review evaluates the existing published series of NIFTP cases, clinical consequences of NIFTP, and emerging changes in the diagnostic criteria for NIFTP. The introduction of NIFTP has resulted in significant impact on the clinical management of thyroid nodules. Recent revisions in the morphological criteria for NIFTP emphasize the need to adhere to very stringent histomorphologic criteria when making a diagnosis of NIFTP. The adoption of NIFTP terminology instead of NI-EFVPC is associated with conservative lobectomy without radioactive iodine treatment in the majority of cases.

PubMed ID: 30953289

Article Size: 3.8 MB

Early squamous cell carcinoma of the oral tongue with histologically benign lymph nodes: A model predicting local control and vetting of the eighth edition of the American Joint Committee on Cancer pathologic T stage.

11JuneLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Interobserver Variability in the Histopathologic Assessment of Extrathyroidal Extension of Well Differentiated Thyroid Carcinoma Supports the New American Joint Committee on Cancer Eighth Edition Criteria for Tumor Staging.

21MayLester D. R. Thompson, MDEndocrine, Thyroid

Turk AT, Asa SL, Baloch ZW, Faquin WC, Fellegara G, Ghossein RA, Giordano TJ, LiVolsi VA, Lloyd R, Mete O, Rosai J, Suster S, Thompson LDR, Wenig BM.

Thyroid. 2019 May;29(5):619-624. doi: 10.1089/thy.2018.0286. Epub 2019 Apr 27.

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

PubMed ID: 30913992

Article Size: 14.3 MB

Rethinking Malignancy Risk in Indeterminate Thyroid Nodules with Positive Molecular Studies: Southern California Permanente Experience.

3MayLester D. R. Thompson, MDEndocrine, Thyroid

Cohen DS, Tongson-Ignacio JE, Lolachi CM, Ghaderi VS, Jahan-Parwar B, Thompson LDR.

Otolaryngol Head Neck Surg. 2019 Apr 23:194599819842859. doi: 10.1177/0194599819842859. [Epub ahead of print]

OBJECTIVES: To recognize that thyroid nodules with atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS; Bethesda III) have different risks of malignancy based on genetic mutation and to consider molecular testing of nodules with AUS/FLUS to help avoid unnecessary morbidity or cost.

STUDY DESIGN: Retrospective cohort study.

SETTING: Multiple locations within Southern California Permanente Medical Group.

SUBJECTS AND METHODS: Patients included those with indeterminate thyroid nodules and AUS/FLUS on 2 separate fine-needle aspirations with positive ThyGenX testing from 2014 to 2017 who underwent thyroid surgery. Patients were classified as having benign or malignant disease. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features was considered benign.

RESULTS: A total of 231 patients had repeat AUS/FLUS with positive molecular testing and surgery. The most frequent type of malignancy was papillary carcinoma, followed by follicular carcinoma. The overall prevalence of malignancy in nodules with mutations was 74.0%, although there was considerable variation: BRAF = 100%, RET = 100%, PAX8-PPARγ = 84.6%, HRAS = 70.7%, HRAS = 63.4%, and KRAS = 33%-a statistically significant finding ( P < .001).

CONCLUSIONS: Not all molecular mutations in thyroid nodules with AUS/FLUS have a high risk of malignancy. Of note, patients with BRAF and RET mutations in our population had a 100% risk of malignancy. Patients with PAX, HRAS, or NRAS mutations had a high risk of malignancy, while patients with KRAS mutations had a lower risk of malignancy. Further studies are needed to determine if the presence of certain molecular mutations can help personalize care and aid in the decision for thyroid surgery.

PubMed ID: 31013183

Article Size: <1 MB

Inter-observer Variability in the Diagnosis of Proliferative Verrucous Leukoplakia: Clinical Implications for Oral and Maxillofacial Surgeon Understanding: A Collaborative Pilot Study.

12AprilLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Thyroid Gland Solitary Fibrous Tumor: Report of 3 Cases and a Comprehensive Review of the Literature

10AprilLester D. R. Thompson, MDEndocrine, Thyroid

Thompson LDR, Wei C, Rooper LM, Lau SK.

Head Neck Pathol. 2019 Dec;13(4):597-605. doi: 10.1007/s12105-019-01012-6. Epub 2019 Feb 13.

Solitary fibrous tumors of the thyroid gland are exceptionally rare. In order to further characterize the clinical and pathologic features of solitary fibrous tumor arising at this anatomic site, three cases of thyroid gland solitary fibrous tumor were analyzed in conjunction with 35 cases compiled from the English literature. Thyroid gland solitary fibrous tumors showed an equal sex distribution with a mean age at presentation of 54.4 years (range, 28-88 years). The patients typically presented with an asymptomatic, slow growing neck mass. Microscopically, the tumors were characterized by cytologically bland spindle cells with patternless growth, hypocellular and hypercellular areas, variable amounts of collagen, and ectatic, branching blood vessels. Two previous reported tumors were considered to be histologically malignant on the basis of increased mitotic activity, profound pleomorphism and tumor necrosis. Immunohistochemically, the tumor cells are variably positive with CD34, bcl-2, and CD99. STAT6 immunohistochemistry, performed on the current cases, demonstrated a strong, diffuse nuclear expression in all tumors. Among 26 patients with available follow up data (mean 47.3 months), one developed local recurrence and distant metastasis. Solitary fibrous tumors occurring in the thyroid gland are uncommon, but can be reliably diagnosed based on the presence of characteristic morphologic features as well as immunohistochemical expression of STAT6 and CD34. The majority of thyroid gland solitary fibrous tumors have exhibited an indolent clinical course, however experience is limited. The rare potential for aggressive clinical behavior requires clinical surveillance.

PubMed ID: 30758754

Article Size: 2.6 MB

Meaningful Value Added by Standardized, Internationally Validated, and Evidence-Based Pathology Data Sets for Cancer Reporting of Head and Neck Sites Coordinated by the International Collaboration on Cancer Reporting.

10AprilLester D. R. Thompson, MDStaging

Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):422-423. doi: 10.5858/arpa.2018-0489-ED.

This is an introduction to the Special Section–Structured Reporting Data Sets for Head and Neck Tumors From the International Collaboration on Cancer Reporting, Part I

PubMed ID: 30920861

Article Size: <1 MB

A Rainbow of Colors and Spectrum of Textures: An Approach to Oral Mucosal Entities.

10AprilLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Genetic Characteristics of Aldosterone-Producing Adenomas in Blacks

12FebruaryLester D. R. Thompson, MDAdrenal, Endocrine

Nanba K, Omata K, Gomez-Sanchez CE, Stratakis CA, Demidowich AP, Suzuki M, Thompson LDR, Cohen DL, Luther JM, Gellert L, Vaidya A, Barletta JA, Else T, Giordano TJ, Tomlins SA, Rainey WE.

Hypertension. 2019 Apr;73(4):885-892. doi: 10.1161/HYPERTENSIONAHA.118.12070.

Somatic mutations have been identified in aldosterone-producing adenomas (APAs) in genes that include KCNJ5, ATP1A1, ATP2B3, and CACNA1D. Based on independent studies, there appears to be racial differences in the prevalence of somatic KCNJ5 mutations, particularly between East Asians and Europeans. Despite the high cardiovascular disease mortality of blacks, there have been no studies focusing on somatic mutations in APAs in this population. In the present study, we investigated genetic characteristics of APAs in blacks using a CYP11B2 (aldosterone synthase) immunohistochemistry-guided next-generation sequencing approach. The adrenal glands with adrenocortical adenomas from 79 black patients with primary aldosteronism were studied. Seventy-three tumors from 69 adrenal glands were confirmed to be APAs by CYP11B2 immunohistochemistry. Sixty-five of 73 APAs (89%) had somatic mutations in aldosterone-driver genes. Somatic CACNA1D mutations were the most prevalent genetic alteration (42%), followed by KCNJ5 (34%), ATP1A1 (8%), and ATP2B3 mutations (4%). CACNA1D mutations were more often observed in APAs from males than those from females (55% versus 29%, P=0.033), whereas KCNJ5 mutations were more prevalent in APAs from females compared with those from males (57% versus 13%, P<0.001). No somatic mutations in aldosterone-driver genes were identified in tumors without CYP11B2 expression. In conclusion, 89% of APAs in blacks harbor aldosterone-driving mutations, and unlike Europeans and East Asians, the most frequently mutated aldosterone-driver gene was CACNA1D. Determination of racial differences in the prevalence of aldosterone-driver gene mutations may facilitate the development of personalized medicines for patients with primary aldosteronism.

PubMed ID: 30739536

Article Size: <1 MB

Radiographic nodal prognostic factors in stage I HPV-related oropharyngeal squamous cell carcinoma.

17DecemberLester D. R. Thompson, MDHead & Neck, Oropharynx

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

The HTN3-MSANTD3 Fusion Gene Defines a Subset of Acinic Cell Carcinoma of the Salivary Gland.

10DecemberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Andreasen S, Varma S, Barasch N, Thompson LDR, Miettinen M, Rooper L, Stelow EB, Agander TK, Seethala RR, Chiosea SI, Homøe P, Wessel I, Larsen SR, Erentaite D, Bishop JA, Ulhøi BP, Kiss K, Melchior LC, Pollack JR, West RB.

Am J Surg Pathol. 2019 Apr;43(4):489-496

The spectrum of tumors arising in the salivary glands is wide and has recently been shown to harbor a network of tumor-specific fusion genes. Acinic cell carcinoma (AciCC) is one of the more frequently encountered types of salivary gland carcinoma, but it has remained a genetic orphan until recently when a fusion between the HTN3 and MSANTD3 genes was described in one case. Neither of these 2 genes is known to be implicated in any other malignancy. This study was undertaken to investigate whether the HTN3-MSANTD3 fusion is a recurrent genetic event in AciCC and whether it is a characteristic of one of its histological variants. Of the 273 AciCCs screened, 9 cases showed rearrangement of MSANTD3 by break-apart fluorescence in situ hybridization, 2 had 1 to 2 extra signals, and 1 had gain, giving a total of 4.4% with MSANTD3 aberrations. In 6 of 7 available cases with MSANTD3 rearrangement, the HTN3-MSANTD3 fusion transcript was demonstrated with real-time polymerase chain reaction . Histologically, all fusion-positive cases were predominantly composed of serous tumor cells growing in solid sheets, with serous tumor cells expressing DOG-1 and the intercalated duct-like cell component being CK7 positive and S-100 positive in 6/9 cases. All but one case arose in the parotid gland, and none of the patients experienced a recurrence during follow-up. In contrast, the case with MSANTD3 gain metastasized to the cervical lymph nodes and lungs. In conclusion, we find the HTN3-MSANTD3 gene fusion to be a recurrent event in AciCC with prominent serous differentiation and an indolent clinical course.

PubMed ID: 30520817

Article Size: <1 MB

Hypothalamic Vasopressin-producing Tumors: Often Inappropriate Diuresis But Occasionally Cushing Disease.

6NovemberLester D. R. Thompson, MDEndocrine, Pituitary

Asa SL, Ezzat S, Kelly DF, Cohan P, Takasumi Y, Barkhoudarian G, Heaney AP, Ridout R, Chik CL, Thompson LDR, Gentili F, Mete O.

Am J Surg Pathol. 2019 Feb;43(2):251-260.

Tumors of hypothalamic neurons that produce vasopressin are rare. We retrieved all cases of vasopressin-positive tumors in the sellar region from the database of the Department of Pathology. Five cases fulfilled the selection criteria, representing the first series of such tumors. Clinical, radiologic, and pathologic features were reviewed. Four tumors classified as neurocytomas were identified in 3 females and 1 male patient; the ages at onset of symptoms ranged from 17 to 40 years. All were large sellar masses with suprasellar extension and/or invasion of the parasellar sinuses. Three patients had the syndrome of inappropriate antidiuresis; in one of these, a 6-year history was initially considered to be idiopathic. One patient died of progressive disease; 3 had incomplete resections and are being followed. In contrast to these patients with neurocytoma, a 65-year-old woman had Cushing disease and a 0.8 cm mass that was completely resected at transsphenoidal surgery; this tumor was a gangliocytoma producing vasopressin associated with corticotroph hyperplasia. We postulate that the small amount of vasopressin secreted by this mature gangliocytic tumor was locally bound to corticotrophs, resulting in hyperplasia and Cushing disease, without sufficient overproduction to cause systemic effects of vasopressin excess. Hypothalamic neurocytoma is a tumor that can mimic pituitary neuroendocrine tumors and olfactory neuroblastoma but is distinguished by positivity for neurofilaments, NeuN, and TTF-1 and negative staining for adenohypophysial biomarkers. Our cases illustrate that neurocytoma and gangliocytoma are 2 variants of tumors of hypothalamic neurons that can produce vasopressin. The morphologic and proliferative features of these 2 tumor types represent 2 ends of a spectrum; their function also can result in divergent clinical manifestations, one characterized by reduced urine output and the other by the more insidious features of glucocorticoid excess.

PubMed ID: 30379651

Article Size: <1 MB

Molecular Profiling of Salivary Gland Intraductal Carcinoma Revealed a Subset of Tumors Harboring NCOA4-RET and Novel TRIM27-RET Fusions: A Report of 17 cases.

12OctoberLester D. R. Thompson, MDHead & Neck, Salivary Gland

Skálová A, Vanecek T, Uro-Coste E, Bishop JA, Weinreb I, Thompson LDR, de Sanctis S, Schiavo-Lena M, Laco J, Badoual C, Santana Conceiçao T, Ptáková N, Baněčkova M, Miesbauerová M, Michal M.

Am J Surg Pathol. 2018 Nov;42(11):1445-1455.

Intraductal carcinoma (IC) is the new World Health Organization designation for tumors previously called “low-grade cribriform cystadenocarcinoma” and “low-grade salivary duct carcinoma.” The relationship of IC to salivary duct carcinoma is controversial, but they now are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with features similar to mammary atypical ductal hyperplasia or ductal carcinoma in situ, that shows diffuse S100 protein and mammaglobin positivity and is only partially defined genetically. (Mammary analogue) secretory carcinoma harboring ETV6-NTRK3, and in rare cases ETV6-RET fusion, shares histomorphologic and immunophenotypical features with IC. Recently, RET rearrangements and NCOA4-RET have been described in IC, suggesting a partial genetic overlap with mammary analogue secretory carcinoma. Here, we genetically characterize the largest cohort of IC to date to further explore this relationship. Seventeen cases of IC were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). Identified fusions were confirmed using fluorescence in situ hybridization break apart and, in some cases, fusion probes, and a reverse transcription polymerase chain reaction designed specifically to the detected breakpoints. All analyzed cases were known to be negative for ETV6 rearrangement by fluorescence in situ hybridization and for ETV6-NTRK3 fusion by reverse transcription polymerase chain reaction. Next-generation sequencing analysis detected a NCOA4-RET fusion transcript joining exon 7 or 8 of NCOA4 gene and exon 12 of RET gene in 6 cases of intercalated duct type IC; and a novel TRIM27-RET fusion transcript between exons 3 and 12 in 2 cases of salivary gland tumors displaying histologic and immunohistochemical features typical of apocrine IC. A total of 47% of IC harbored a fusion involving RET. In conclusion, we have confirmed the presence of NCOA4-RET as the dominant fusion in intercalated duct type IC. A novel finding in our study has been a discovery of a subset of IC patients with apocrine variant IC harboring a novel TRIM27-RET.

PubMed ID: 30045065

Article Size: <1 MB

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients.

8OctoberLester D. R. Thompson, MDEar & Temporal Bone, Head & Neck

Thompson LDR, Magliocca KR, Andreasen S, Kiss K, Rooper L, Stelow E, Wenig BM, Bishop JA.

Head Neck Pathol. 2019 Sep;13(3):355-363. doi: 10.1007/s12105-018-0973-8. Epub 2018 Oct 5.

Endolymphatic sac tumors (ELSTs) are rare, slowly growing temporal bone neoplasms which show a high association with von Hippel-Lindau (VHL) syndrome. The immunohistochemistry evaluation of these papillary-cystic neoplasms frequently raises the differential diagnosis with renal cell carcinoma, among other metastatic neoplasms, whether in VHL patients or not. A cohort of 26 patients with ELSTs were evaluated for histologic features, immunohistochemistry findings, and association with VHL. Standard immunohistochemistry evaluation was performed. Sixteen females and 10 males ranging in age from 10 to 69 years (mean 44; VHL mean: 32) at initial presentation, comprised the cohort of patients. Most (86%) experienced hearing changes or inner ear symptoms (vertigo, dizziness), with an average duration of symptoms for 39 months (range 2-240 months). The tumors were an average of 2.9 cm (range 0.4-8 cm), with 14 left, 11 right sided and one bilateral tumor. Nine patients had documented VHL, with 3 patients having a concurrent or subsequent clear cell renal cell carcinoma. Patients were followed an average of 6.2 years (available in 24 patients): 19 alive without disease, 7.5 years; 2 dead without disease, 1.2 years; and 3 alive with disease, 3.1 years. The neoplastic cells show the following immunohistochemistry findings: AE1/AE3, EMA, CK7, CAIX, GLUT1, VEGF: 100% of cases tested were positive; pax-8: 85% of cases positive; CD10 and RCC: 0% of cases reactive. Based on this cohort of 26 patients with ELST, 9 of whom had VHL, the strong pax-8 and CAIX should be used in conjunction with negative CD10 and RCC to help exclude a metastatic renal cell carcinoma. As CAIX is an enzyme overexpressed in hypoxia and hypoxia inducible factor is what VHL protein regulates, this is an expected, although previously unreported finding. Whether part of VHL or not, VHL mutations may be a somatic rather than germline finding in the tumors, a possible further explanation for the CAIX reaction.

PubMed ID: 30291511

Article Size: 2 MB

Sinonasal renal cell-like adenocarcinomas: robust carbonic anhydrase expression

19SeptemberLester D. R. Thompson, MDHead & Neck, Sinonasal Tract

Shen T, Shi Q, Velosa CM, Bai S, Thompson LDR, Keen C, Patel A, Simpson R, Wei S, Brandwein-Gensler M. Sinonasal Renal Cell-Like Adenocarcinomas: Robust Carbonic Anhydrase Expression and the Renal-Like Function of Schneiderian Mucosa

Hum Pathol. 2015 Nov;46(11):1598-606.

We report 3 new patients with sinonasal renal cell-like adenocarcinoma (SNRCLA). One case submitted in consultation demonstrated robust carbonic anhydrase IX (CA-IX) expression, leading us to a broader inquiry of CA-IX and carbonic anhydrase II (CA-II) expression in other SNRCLA, Schneiderian tissues, and histologic mimickers. Robust cytoplasmic and membranous CA-IX expression is demonstrated in 6 of 7 SNRCLAs; CA-II expression was demonstrated in 2 of 5 cases. Robust, diffuse CA-II expression is demonstrated throughout sinonasal seromucinous glands in all 10 normal Schneiderian samples. CA-IX is also expressed in all normal sinonasal samples, albeit focally. The closest salivary mimic to SNRCLA is hyalinizing salivary clear cell carcinoma; only focal CA-IX expression was demonstrated in 1 of 2 cases studied. Carbonic anhydrase expression in Schneiderian tissue speaks to its role in regulating the ion concentration of sinonasal secretions and may also explain the origin of this rare tumor.

PubMed ID: 26299508

Article Size: 4.7 MB

ExpertPath and ImmunoQuery Webinar given by Dr. Lester D.R. Thompson

17SeptemberLester D. R. Thompson, MDMedical Techniques, Videos

TIP: For sharpest focus, you may need to change YouTube’s default quality settings from Auto to 1080p60. Once you start the video, click the Settings cog icon near the lower right corner of video frame, select Quality and change Auto to 1080p. You should also click the Full Screen icon at the far right.

ExpertPath and ImmunoQuery Webinar - Dr Lester D.R. Thompson

ExpertPath and ImmunoQuery are trademarked by their respective companies.

Carcinomas of the Oral Cavity (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Müller S, Boy S, Day TA, Magliocca K, Richardson MS, Sloan P, Tilakaratne WM, Zain RB, Thompson LDR.

(2018) Carcinomas of the Oral Cavity, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-19-4

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of invasive carcinomas of the oral cavity, including lip and tongue. Mucosal melanoma, lymphomas and sarcomas are not included. In addition, neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable.

EXPERT COMMITTEE:

* Chair – Susan Müller, USA
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Sonja Boy, South Africa
* Terrance Day, USA
* Kelly Magliocca, USA
* Mary Richardson, USA
* Philip Sloan, UK
* WM Tilakaratne, Sri Lanka
* Rosnah B Zain, USA

ISBN: 978-1-925687-19-4

Article Size: 1.6 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Oral Cavity Carcinomas: Explanations and Recommendations of the Guidelines From the International Collaboration of Cancer Reporting.

Müller S, Boy S, Day TA, Magliocca K, Richardson MS, Sloan P, Tilakaratne WM, Zain RB, Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):439-446. doi: 10.5858/arpa.2018-0411-SA. Epub 2018 Nov 30.

PubMed ID: 30500296

Article Size: 3.3 MB

Mucosal Melanomas of the Head and Neck (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Thompson LDR, Franchi A, Helliwell T, Müller S, Williams MD.

(2018) Mucosal Melanomas of the Head and Neck, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-25-5

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of mucosal melanoma arising in the nasopharynx, oropharynx, larynx, hypopharynx, oral cavity, nasal cavity and paranasal sinuses. All other malignancies and tumour categories are dealt with in separate datasets, specifically cutaneous melanoma is separately reported. Direct extension of a cutaneous primary into a mucosal site should be excluded, and would not be reported in this dataset. Metastasis to a head and neck mucosal site is also excluded. Neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable.

EXPERT COMMITTEE:

* Chair and Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Alessandro Franchi, Italy
* Tim Helliwell, UK
* Susan Müller, USA
* Michelle Williams, USA

ISBN: 978-1-925687-25-5

Article Size: 1.2 MB

View article: Histopathology Reporting Guide

View article: Data Set for Reporting of Mucosal Melanomas of the Head and Neck: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Williams MD, Franchi A, Helliwell T, Müller S, Thompson LDR.

Arch Pathol Lab Med. 2019 May;143(5):603-609 doi: 10.5858/arpa.2018-0412-SA.

PubMed ID: 30500297

Article Size: 4.8 MB

Carcinomas of the Nasopharynx and Oropharynx (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Oropharynx, Staging

Lewis JS Jr, Adelstein DJ, Agaimy A, Diane Carlson D, Faquin WC, Helliwell T, Hille J, Nicholls JM, Ng T, O’Sullivan B, Thompson LDR.

(2018) Carcinomas of the Nasopharynx and Oropharynx, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-18-7

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of the nasopharynx and oropharynx. The protocol applies to all invasive carcinomas of the nasopharynx and oropharynx including the base of tongue, tonsils, soft palate, posterior wall, and uvula. Lymphomas and sarcomas are not included. Neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable.

EXPERT COMMITTEE:

* Chair – James S Lewis Jr, USA
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* David Adelstein, USA
* Abbas Agaimy, Germany
* Diane Carlson, USA
* William Faquin, USA
* Tim Helliwell, UK
* Jos Hille, South Africa
* John Nicholls, Hong Kong
* Tony Ng, Canada
* Brian O’Sullivan, Canada

ISBN: 978-1-925687-18-7

Article Size: 1.5 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Carcinomas of the Nasopharynx and Oropharynx: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Lewis JS Jr, Adelstein DJ, Agaimy A, Diane Carlson D, Faquin WC, Helliwell T, Hille J, Nicholls JM, Ng T, O’Sullivan B, Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):447-451. doi: 10.5858/arpa.2018-0405-SA. Epub 2018 Nov 30.

PubMed ID: 30500294

Article Size: 2 MB

Carcinomas of the Nasal Cavity and Paranasal Sinuses (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Franchi A, Bishop JA, Coleman H, Flucke U, Licitra L, Llorente JL, Stelow E, Toner M, Weinreb I, Thompson LDR.

(2018) Carcinomas of the Nasal Cavity and Paranasal Sinuses, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-20-0

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of mucosal malignancies originating in the nasal cavities and paranasal sinuses. Neuroectodermal neoplasms (including melanoma) and sarcomas are not included. Bone, soft tissue and lymphoma protocols are separately listed. Neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable. For additional independent tumours, complete a separate dataset for each.

EXPERT COMMITTEE:

* Chair – Alessandro Franchi, Italy
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Justin Bishop, USA
* Hedley Coleman, Australia
* Uta Flucke, Netherlands
* Lisa Licitra, Italy
* José L Llorente, Spain
* Edward Stelow, USA
* Mary Toner, UK
* Ilan Weinreb, Canada

ISBN: 978-1-925687-20-0

Article Size: 1.3 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Carcinomas of the Nasal Cavity and Paranasal Sinuses: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Franchi A, Bishop JA, Coleman H, Flucke U, Licitra LF, Pendás JLL, Stelow EB, Toner M, Weinreb I, Wenig BM, Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):424-431. doi: 10.5858/arpa.2018-0404-SA. Epub 2018 Nov 30

PubMed ID: 30500298

Article Size: 2 MB

Carcinomas of the Hypopharynx, Larynx and Trachea (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Helliwell T, Chernock R, Dahlstrom JE, Gale N, McHugh J, Perez-Ordonez B, Roland N, Zidar N, Thompson LDR.

(2018) Carcinomas of the Hypopharynx, Larynx and Trachea, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-17-0

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of mucosal malignancies of the larynx, hypopharynx and trachea. The protocol applies to all invasive carcinomas of the larynx, hypopharynx and trachea (including the supraglottis, glottis, and subglottis). Salivary-type malignancies arising from mucosal glands of the hypopharynx and larynx should be recorded in this dataset. Mucosal melanoma is presented in a separate dataset. Lymphomas and sarcomas are not included. Malignancies arising at other sites in the head and neck region, and neck dissections and nodal excisions are dealt with in separate datasets which may be used, as appropriate, in conjunction with this dataset. Where more than one anatomically or histologically distinct primary tumours occur, a separate dataset should be completed for each tumour.

EXPERT COMMITTEE:

* Chair – Tim Helliwell, UK
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Rebecca Chernock, USA
* Jane Dahlstrom, Australia
* Nina Gale, Slovenia
* Jonathan McHugh, USA
* Bayardo Perez-Ordonez, Canada
* Nick Roland, UK
* Nina Zidar, Slovenia

ISBN: 978-1-925687-17-0

Article Size: 1.5 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Carcinomas of the Hypopharynx, Larynx, and Trachea: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting (ICCR).

Helliwell T, Chernock R, Dahlstrom JE, Gale N, McHugh J, Perez-Ordonez B, Roland N, Zidar N, Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):432-438. doi: 10.5858/arpa.2018-0419-SA. Epub 2018 Nov 30.

PubMed ID: 30500292

Article Size: 2 MB

Ear and Temporal Bone Tumours (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Thompson LDR, Gupta R, Sandison A, Wenig BM.

(2018) Ear and Temporal Bone Tumours, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-22-4

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of the ear and temporal bone. It includes ONLY primary tumours of the external auditory canal, middle and inner ear, including both benign and malignant entities (specifically due to anatomic confines and management alternatives which may require significant, destructive or disfiguring surgery).

By definition, all malignancies of the external ear (pinna, concha, scaphoid, lobe, etc., such as squamous cell carcinoma, basal cell carcinoma, atypical fibroxanthoma, Merkel cell carcinoma and melanoma) are separately covered by the dermatopathology datasets.

Neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable. For bilateral tumours, a separate dataset should be completed for each tumour.

EXPERT COMMITTEE:

* Chair and Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Ruta Gupta, Australia
* Ann Sandison, UK
* Bruce Wenig, USA

ISBN: 978-1-925687-22-4

Article Size: 1.4 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Ear and Temporal Bone Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Gupta R, Sandison A, Wenig BM, Thompson LDR.

Arch Pathol Lab Med. 2019 May;143(5):593 602. doi: 10.5858/arpa.2018-0415-SA.

PubMed ID: 30500288

Article Size: 4.7 MB

Carcinomas of the Major Salivary Glands (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Seethala RR, Altemani A, Ferris RL, Fonseca I, Gnepp DR, Ha P, Nagao T, Skalova A, Stenman G, Thompson LDR.

(2018) Carcinomas of the Major Salivary Glands, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-21-7

SCOPE:

The dataset has been developed for the reporting of resection and biopsy specimens of malignant neoplasms and associated carcinoma in situ arising from the major salivary glands. The protocol applies to all carcinomas of the parotid, submandibular and sublingual glands. Melanomas, lymphomas, and sarcomas are dealt with in separate datasets. Minor salivary gland malignancies arising in the oral cavity, nasal cavity and paranasal sinuses, trachea, nasopharynx, oropharynx and hypopharynx and odontogenic specimens are staged according to their anatomical sub-site and are dealt with in separate datasets. In addition, neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable. For bilateral tumours, a separate dataset should be completed for each tumour.

EXPERT COMMITTEE:

* Chair – Raja Seethala, USA
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Albina Altemani, Brazil
* Robert L Ferris, USA
* Isabel Fonseca, Portugal
* Douglas Gnepp, USA
* Patrick Ha, USA
* Toshitaka Nagao, Japan
* Alena Skalova, Czech Republic
* Göran Stenman, Sweden

ISBN: 978-1-925687-21-7

Article Size: 1.3 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Carcinomas of the Major Salivary Glands: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting.

Seethala RR, Altemani A, Ferris RL, Fonseca I, Gnepp DR, Ha P, Nagao T, Skalova A, Stenman G, Thompson LDR.

Arch Pathol Lab Med. 2019 May;143(5):578-586. doi: 10.5858/arpa.2018-0422-SA.

PubMed ID: 30500293

Article Size: 3.4 MB

Malignant Odontogenic Tumours (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Odell E, Baumhoer D, Carlos R, Hunter KD, Mosqueda-Taylor A, Richardson M, Slater L, Slootweg PJ, Speight P, Wright J, Thompson LDR.

(2018) Malignant Odontogenic Tumours, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-23-1

SCOPE:

The dataset has been developed for the reporting of biopsy and resection specimens for malignant primary odontogenic tumours. Malignant neoplasms arising in the nasal cavity and paranasal sinuses, oral cavity, salivary glands, trachea, pharynx and larynx are dealt with in separate datasets. Bone, soft tissue and lymphoma protocols will be separately listed. In addition, neck dissections and nodal excisions are dealt with in a separate dataset, and this dataset should be used in conjunction, where applicable.

EXPERT COMMITTEE:

* Chair – Edward Odell, UK
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Daniel Baumhoer, Switzerland
* Roman Carlos, Guatemala
* Keith Hunter, UK
* Adalberto Mosqueda-Taylor, Mexico
* Mary Richardson, USA
* Lee Slater, USA
* Pieter Slootweg, Netherlands
* Paul Speight, UK
* John Wright, USA

ISBN: 978-1-925687-23-1

Article Size: 1.3 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Malignant Odontogenic Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting (ICCR).

Slootweg PJ, Odell EW, Baumhoer D, Carlos R, Hunter KD, Taylor AM, Richardson MS, Slater L, Speight PM, Wright J, Thompson LDR.

Arch Pathol Lab Med. 2019 May;143(5):587-592. doi: 10.5858/arpa.2018-0417-SA.

PubMed ID: 30500289

Article Size: 2.9 MB

Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours (TNM8)

12SeptemberLester D. R. Thompson, MDHead & Neck, Staging

Bullock M, Beitler JJ, Carlson DL, Fonseca I, Hunt J, Katabi N, Sloan P, Taylor SM, Williams MD, Thompson LDR.

(2018) Nodal Excisions and Neck Dissection Specimens for Head & Neck Tumours, Histopathology Reporting Guide, 1st Edition. International Collaboration on Cancer Reporting; Sydney, Australia. ISBN: 978-1-925687-24-8

SCOPE:

The dataset has been developed for the reporting of lymph node resections from patients with carcinomas and melanomas of the head and neck. This excludes nodal resections for lymphoma and sarcomas. It is not intended for use in reporting lymph node core biopsy or fine needle aspirations. Carcinomas covered by the dataset include squamous cell carcinomas, sinonasal carcinomas, salivary and non-salivary type adenocarcinomas and neuroendocrine tumours. Pathologists may also apply the dataset to metastatic non-Merkel cutaneous squamous cell carcinomas and other cutaneous carcinomas. This dataset is to be used in conjunction with other datasets in the Head and Neck Series.

EXPERT COMMITTEE:

* Chair – Martin Bullock, Canada
* Series Champion – Lester Thompson, USA

DOMAIN EXPERTS:

* Jonathan Beitler, USA
* Diane L. Carlson, USA
* Isabel Fonseca, Portugal
* Jennifer Hunt, USA
* Nora Katabi, USA
* Philip Sloan, UK
* S. Mark Taylor, Canada
* Michelle Williams, USA

ISBN: 978-1-925687-24-8

Article Size: 2 MB

View article: Histopathology Reporting Guide

View article: Data Set for the Reporting of Nodal Excisions and Neck Dissection Specimens for Head and Neck Tumors: Explanations and Recommendations of the Guidelines From the International Collaboration on Cancer Reporting (ICCR).

Bullock M, Beitler JJ, Carlson DL, Fonseca I, Hunt J, Katabi N, Sloan P, Taylor SM, Williams MD, Thompson LDR.

Arch Pathol Lab Med. 2019 Apr;143(4):452-462. doi: 10.5858/arpa.2018-0421-SA. Epub 2018 Nov 30.

PubMed ID: 30500291

Article Size: 4.8 MB

Comparison of high-dose Cisplatin-based chemoradiotherapy and Cetuximab-based bioradiotherapy for p16-positive oropharyngeal squamous cell carcinoma in the context of revised HPV-based staging

8SeptemberLester D. R. Thompson, MDHead & Neck, Oropharynx

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

Ectomesenchymal Chondromyxoid Tumor: A Neoplasm Characterized by Recurrent RREB1-MKL2 Fusions.

14JulyLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): Achieving Better Agreement by Refining Diagnostic Criteria

28MayLester D. R. Thompson, MDEndocrine, Thyroid

Alves VAF, Kakudo K, LiVolsi V, Lloyd RV, Nikiforov YE, Nosé V, Papotti M, Thompson LDR.

Clinics (Sao Paulo). 2018 May 21;73:e576.

FIRST PARAGRAPH: Over the past decade, improvements in imaging technologies along with greater access to medical care have resulted in the discovery of neoplasms in a much earlier stage. This has contributed to a reduction in cancer mortality. However, an unintended consequence of early detection has been detection of lesions which present at an earlier pathologic stage of development, requiring modification of diagnostic criteria, as well as determining a more appropriate risk stratification to inform management.

PubMed ID: 29791602

Article Size: <1 MB

Measuring Depth of Invasion in Early Squamous Cell Carcinoma of the Oral Tongue: Positive Deep Margin, Extratumoral Perineural Invasion, and Other Challenges.

28MayLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Diagnostic Approach to Fine Needle Aspirations of Cystic Lesions of the Salivary Gland

28MayLester D. R. Thompson, MDHead & Neck, Salivary Gland

Pantanowitz L , Thompson LDR, Rossi ED.

Head Neck Pathol. 2018 Dec;12(4):548-561.

Fine needle aspiration (FNA) has diagnostic and therapeutic value in the management of salivary gland cysts. Rendering an accurate diagnosis from an aspirated salivary gland cyst is challenging because of the broad differential diagnosis, possibility of sampling error, frequent hypocellularity of specimens, morphologic heterogeneity, and overlapping cytomorphology of many cystic entities. To date, there have been no comprehensive review articles providing a practical diagnostic approach to FNA of cystic lesions of salivary glands. This article reviews the cytopathology of salivary gland cysts employing 2017 World Health Organization terminology, addresses the accuracy of FNA, and presents The Milan System approach for reporting in cystic salivary gland cases. The utility of separating FNA specimens from salivary gland cysts, based upon the presence of mucin and admixed lymphocytes in cyst fluid is demonstrated. A reliable approach to interpreting FNA specimens from patients with cystic salivary gland lesions is essential to accurately determine which of these patients may require subsequent surgery.

PubMed ID: 29524082

Article Size: 3.5 MB

Dentigerous cyst

28MayLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

Article Size: <1 MB

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in thyroid tumor classification.

3MayLester D. R. Thompson, MDEndocrine, Thyroid

Kakudo K, El-Naggar AK, Hodak SP, Khanafshar E, Nikiforov YE, Nosé V, Thompson LDR.

Pathol Int. 2018 Jun;68(6):327-333.

In 2016, a new morphological thyroid tumor entity, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), was introduced to replace a group of lowrisk tumors known as noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). Since then, there have been more than 60 publications with a keyword of NIFTP according to a PubMed literature survey on October 28, 2017. These publications cover many aspects on this new tumor entity, cytological diagnosis, ultrasound features, molecular genotyping, clinical management and long-term outcome of NIFTP patients. They supported an indolent nature of NIFTP even in large size (>4 cm) tumors. Under ultrasound examination, NIFTPs are usually in low-suspicion nodules while invasive EFVPTC in intermediate-suspicious nodules and infiltrative FVPTCs in high-suspicion nodules. In FNA cytology, the majority of NIFTP are classified in indeterminate (atypia of uncertain significance/follicular lesion of uncertain significance, follicular neoplasm/suspicious for follicular neoplasm or suspicious for malignancy) categories. The new 4th edition of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs including thyroid tumors was published in 2017 and it incorporated a new chapter on borderline tumors of follicular cell origin. These included hyalinizing trabecular tumor, uncertain malignant potential (UMP), and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). UMP and NIFTP were incorporated as subchapters in a new chapter of other encapsulated follicular-patterned thyroid tumors (Table 1). Their behavior codes were set as /1 (unspecified, borderline, or uncertain behavior), and not /0 (benign tumors), /2 (carcinoma in situ and grade III intraepithelial neoplasia), or /3 (malignant tumors).

This editorial was written by seven authors, on behalf of all authors of the NIFTP working group, to refine diagnostic criteria for NIFTP in order to improve concordance in the diagnosis and to address several issues with the diagnosis of NIFTP raised in recent publications.

PubMed ID: 29675873

Article Size: <1 MB

Head and Neck Kaposi Sarcoma: Clinicopathological Analysis of 11 Cases.

13MarchLester D. R. Thompson, MDHead & Neck, Oral Cavity/Gnathic (Jaw)

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

An International Interobserver Variability Reporting of the Nuclear Scoring Criteria to Diagnose Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: a Validation Study

9MarchLester D. R. Thompson, MDEndocrine, Thyroid

Thompson LDR, Poller DN, Kakudo K, Burchette R, Nikiforov YE, Seethala RR.

Endocr Pathol. 2018 Sep;29(3):242-249.

The aim of the study was to assess interobserver variation in reporting nuclear features of encapsulated follicular variant of papillary thyroid carcinoma, newly reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), based on a proposed standardized scoring system. An education module was individually reviewed as a pre-evaluation teaching guide of the specific features of classical papillary carcinoma, the specific inclusion and exclusion features for the diagnosis of NIFTP, and a catalog of the standardized scoring system of the nuclear features of papillary carcinoma used to reach this diagnosis. Participants subsequently reviewed 30 cases of thyroid lesions previously scored by members of the Endocrine Pathology Society Working Group for the Re-evaluation of the Encapsulated Follicular Variant of Papillary Thyroid Carcinoma. There was one uninvolved reference image to demonstrate fixation, processing, and cell size and one image from each case for scoring, with results recorded for each participant. The location of training (country and program), years as a practicing pathologist, and approximate number of thyroid gland surgical cases diagnosed per year were recorded. The degree of agreement between participants was assessed by kappa statistics, using the individual criteria and the average composite scores of the Working Group as a point of comparison. Using the Nuclear Standardized Scoring System, the interobserver agreement for final diagnosis score was generally excellent: unweighted and weighted kappa values between individual observers ranging from 0.242 to 0.930 (average 0.626). There was significant agreement between observers in reaching an interpretation of the presence or absence of nuclear features to diagnose NIFTP (score 0–1 versus score of 2–3), with California pathologists, 0.63 (median 0.66, SD 0.15); Japanese pathologists, 0.64 (median 0.66, SD 0.16); and UK pathologists, 0.60 (median 0.57, SD 014) compared to the expert panel, 0.70 (median 0.73, SD 0.19). The use of the nuclear scoring system to evaluate the nuclear features of papillary thyroid carcinoma as applied to reach the diagnosis of NIFTP shows a good to substantial interobserver agreement, suggesting that consensus can be reached in diagnosing the nuclear features required for this newly reclassified neoplasm.

PubMed ID: 29508145

Article Size: 2 MB