Pathologic reporting of Tall Cell Variant of Papillary Thyroid Cancer: Have we reached a consensus?

Hernandez-Prera J, Machado R, Asa SL, Baloch ZW, Faquin WC, Ghossein R Md, LiVolsi VA, Lloyd RV, Mete O, Nikiforov YE, Seethala R, Suster S, Thompson LDR, Turk A, Sadow PM, Urken ML, Wenig BM.
Thyroid. 2017 Oct 12. [Epub ahead of print]
BACKGROUND: Tall cell variant (TCV) is widely believed to be a more aggressive subtype of papillary thyroid carcinoma (PTC). Despite the significance of TCV with respect to risk stratification and therapeutic decision making, its diagnosis is subject to interobserver variability. We aim to determine the level of agreement among expert pathologists in the identification and reporting of TCV.
METHODS: 17 surgical resections for thyroid cancer containing the diagnostic term “tall cell” in their pathology reports and 22 cases diagnosed as classical PTC were selected. Cases were digitalized and 14 expert pathologists reviewed the scanned slides blinded to the original interpretation. Each pathologist designated each case as TCV or not and answered multiple questions about diagnostic histopathologic features of TCV.
RESULTS: The overall strength of agreement for identifying TCV was fair (Fleiss kappa 0.34) and the proportion of observed agreement was 0.70. Fifteen out of twenty-two (68%) cases originally diagnosed as PTC classical variant were re-classified as TCV by at least one expert pathologist. It was noted that four different definitions for TCV were used by the participants based on various combinations of cell height to width (H:W) ratio and the percentage of tumor cells showing that specific ratio. All pathologists agreed that the diagnosis of TCV does not rely solely on a specific H:W ratio.
CONCLUSIONS: Pathologic reporting of TCV varies among pathologists. This disagreement is a result of the lack of unanimous diagnostic criteria and variation in individual pathologists’ interpretations. These discrepancies lead to over- and under-diagnosis of TCV, which has significant implications in patient management. It is imperative to understand this variability in diagnosis TCV as it relates to risk stratification and interpretation of clinical studies related to this histologic subtype of PTC. Further studies are needed to reach consensus on the diagnostic criteria of TCV.
PubMed ID: 29020884

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

Seethala RR, Baloch ZW, Barletta JA, Khanafshar E, Mete O, Sadow PM, LiVolsi VA, Nikiforov YE, Tallini G, Thompson LD.
Mod Pathol. 2017 Oct 20.
The rising incidence of papillary thyroid carcinoma is linked in part to inclusion of noninvasive follicular variant of papillary thyroid carcinoma. Despite its designation as carcinoma, noninvasive follicular variant of papillary thyroid carcinoma appears to be exceptionally indolent, often over treated by current treatment practices. Additionally, criteria for diagnosis have historically been subjective and challenging. Recently, an international multidisciplinary collaborative group performed a clinicopathologic survey of such cases with extended follow-up and concluded based on the outcome data that a revision in nomenclature was warranted, proposing ‘Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).’ This monograph is a synopsis and guide for pathologists on NIFTP and focuses on histologic features, including inclusion and exclusion criteria used to define NIFTP, as well as grossing guidelines, reporting practices, and potential diagnostic limitations.
PubMed ID: 29052599
Article Size: 10 MB

Long-term follow-up of a patient with malignant transformation of inverted papilloma into sinonasal undifferentiated carcinoma.

Orgain CA, Shibuya TY, Thompson LD, Keschner DB, Garg R, Lee JT.
Allergy Rhinol (Providence). 2017 Oct 1;8(3):173-177.
INTRODUCTION: Inverted papillomas (IP) are benign sinonasal neoplasms, which account for 0.5-4% of all nasal tumors. IPs have been known to transform into squamous cell carcinoma in 5-15% of cases. Rarely, transformations to other malignancies have been reported. Here we report a unique case of malignant transformation of an IP into sinonasal undifferentiated carcinoma (SNUC).
METHODS: A case report with a literature review; institutional review board exempted. The clinical presentation, radiographic features, surgical intervention, histopathologic analysis, treatment, and outcome of the case were examined.
RESULTS: A 62-year-old man presented with a 3-month history of nasal airway obstruction, rhinorrhea, and postnasal drip refractory to medical therapy. He had a long history of exposure to fumes, chemicals, dusts, and solvents as a professional painter as well as a 45 pack-year history of smoking and alcohol abuse. The patient was ultimately found to have a left ethmoidal IP with a focus of malignant transformation into SNUC. Endoscopic resection was performed, followed by concurrent chemoradiation and adjuvant chemotherapy. After surgery, he had no evidence of recurrent disease after 9 years of follow-up.
CONCLUSIONS: IP is known to transform into squamous cell carcinoma. Here we report a rare case of malignant transformation into SNUC, a much more uncommon and aggressive lesion. Although traditionally associated with a poorer prognosis, the positive outcome for SNUC observed in this patient may potentially be attributed to early detection and timely therapeutic intervention.
PubMed ID: 29070275
Article Size: 1 MB

Ear fetal rhabdomyoma.

Thompson LD.
Ear Nose Throat J. 2017 Sep;96(9):358.
FIRST PARAGRAPH: Rhabdomyomas are a group of benign tumors that show skeletal muscle differentiation. They are divided into cardiac and extracardiac types with the extracardiac type divided into adult, fetal, and genital types. The fetal type is separated into myxoid and intermediate types. There is a predominance in the head and neck of both the fetal and adult types. The fetal type is commonly seen in newborns and early childhood, with a moderate male predominance (2:1).
PubMed ID: 28931187
Article Size: <1 MB

Improving margin revision: Characterization of tumor bed margins in early oral tongue cancer.

Prabhu AV, Sturgis CD, Lai C, Maxwell JH, Merzianu M, Hernandez-Prera JC, Purgina B, Thompson LDR, Tuluc M, Yang X, Seethala RR, Ferris RL, Chiosea SI.
Oral Oncol. 2017 Oct 24. pii: S1368-8375(17)30319-6.
OBJECTIVES: To improve margin revision, this study characterizes the number, fragmentation, and orientation of tumor bed margins (TBM) in patients with pT1-2 pN0 squamous cell carcinoma (SCC) of the oral tongue.
MATERIALS AND METHODS: Pathology reports (n=346) were reviewed. TBM parameters were indexed. In Group 1 patients all margins were obtained from the glossectomy specimen and there were no TBM. In Revision Group/Group 2 (n=103), tumor bed was sampled to revise suboptimal margins identified by examination of the glossectomy specimen. In Group 3 (n=124), TBM were obtained before examination of the glossectomy specimen.
RESULTS AND CONCLUSIONS: Fewer TBMs were obtained per patient in Group 2 compared to Group 3 (57/103, 55% of patients with <3 vs. 117/124, 94%, ≥3 TBMs, respectively). The new margin surface was more frequently indicated in Group 2 compared to Group 3 (59/103, 57%, vs. 19/124, 15%, p<.001). If glossectomy specimen margins are accepted as the reference standard, then the TBM was 15% sensitive in Group 2 (95% confidence interval [CI], 7-29) and 32% sensitive in Group 3 (95% CI, 15-55). TBM fragmentation (23/103, 22% vs. 42/124, 34%) and frozen vs. permanent discrepancies (8/103, 3% vs. 3/124, 2%) were similar between Groups 2 and 3. The new margin surface was not indicated in 6 of 11 cases with discrepant frozen vs. permanent pathology findings, precluding judgment on final margin status. To facilitate the assessment of final margins, TBM should be represented by one tissue fragment with a marked new margin surface.
PubMed ID: 29074194
Article Size: <1 MB

Sinonasal Tract Alveolar Rhabdomyosarcoma in Adults: A Clinicopathologic and Immunophenotypic Study of Fifty-Two Cases with Emphasis on Epithelial Immunoreactivity.

Thompson LDR, Jo VY, Agaimy A, Llombart-Bosch A, Morales GN, Machado I, Flucke U, Wakely PE Jr, Miettinen M, Bishop JA.
Head Neck Pathol. 2017 Sep 5. [Epub ahead of print]
Sinonasal tract (SNT) alveolar rhabdomyosarcoma (ARMS) are frequently misdiagnosed, especially in adults. Fifty-two adult (≥18 years) patients with SNT ARMS were reviewed and characterized by immunohistochemistry and molecular studies. Twenty-six females and 26 males (18-72 years; mean 43.2 years), presented after a short duration (mean 2.6 months) with a large (mean 5.5 cm) destructive nasal cavity mass, involving multiple contiguous paranasal sites (n = 46) and with cervical adenopathy (n = 41). The tumors showed an alveolar, nested to solid growth pattern below an intact, but often involved (n = 9) epithelium with frequent necrosis (n = 37), destructive bone invasion (n = 30), and lymphovascular invasion (n = 25). The neoplastic cells were dyshesive and dilapidated, with crush artifacts. Rhabdoid features (n = 36) and tumor cell multinucleation (n = 28) were common. Mitotic counts were high (mean 17/10 HPFs). The neoplastic cells showed the following immunohistochemical positive findings: desmin (100%), myogenin (100%), MYOD1 (100%), MSA (96%), SMA (52%), CAM5.2 (50%), AE1/AE3 (36%); other positive markers included S100 protein (27%), CD56 (100%), synaptophysin (35%), and chromogranin (13%). Overall, 54% show epithelial marker reactivity. Molecular studies showed FOXO1 translocations (81%) with PCR demonstrating PAX3 in 72.7% tested. Patients presented with high stage (IV 24; III 26) and metastatic disease (lymph nodes n = 41; distant metastases n = 25) (IRSG grouping). Surgery (n = 16), radiation (n = 41) and chemotherapy (n = 45) yielded an overall survival of 36.1 months (mean; range 2.4-286); 18 alive without disease (mean 69.6 months); 7 alive with disease (mean 11.0 months); 1 dead without disease (63.7 months); and 26 dead with disease (mean 18.5 months). SNT ARMS frequently present in adults as a large, destructive midline mass of short symptom duration, with high stage disease. The alveolar to solid pattern of growth of cells with rhabdoid-plasmacytoid features suggests the diagnosis, but epithelial immunohistochemistry markers are present in 54% of cases, leading to misdiagnosis as carcinomas if muscle markers are not also performed. Overall survival of 36.1 months is achieved with multimodality therapy, but 64% have incurable disease (16.9 months). Mixed anatomic site (p = 0.02) was a significant adverse prognostic indicator, while stage (0.06) and tumor size >5 cm (0.06) approached marginal significance.
PubMed ID: 28875443
Article Size: 4 MB

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma.

Chiosea S, Asa SL, Berman MA, Carty SE, Currence L, Hodak S, Nikiforov YE, Richardson MS, Seethala RR, Sholl LM, Thompson LD, Wenig BM, Worden F1; Members of the Cancer Biomarker Reporting Committee, College of American Pathologists.
Arch Pathol Lab Med. 2017 Apr;141(4):559-563. [Epub 2016 Sep 28.]
FIRST PARAGRAPH: The College of American Pathologists (CAP) offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The CAP regards the reporting elements in the templates as important elements of the biomarker test report, but the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.
PubMed ID: 27681332
Article Size: <1 MB

Metastases to the Parathyroid Glands: A Comprehensive Literature Review of 127 Reported Cases.

Bauer JL, Toluie S, Thompson LDR.
Head Neck Pathol. 2017 Sep 5. [Epub ahead of print]
Metastases to the head and neck organs are uncommon, potentially representing the initial presentation of an occult malignancy. Single case reports and small series report metastases to the parathyroid gland, but there is no large review of the literature on secondary tumors involving the parathyroid glands. A review of the English literature between 1950 and 2017 was performed of all metastases or secondary involvement of the parathyroid glands. One hundred and twenty-seven cases of metastatic tumors were reported, although potentially significantly unrepresented in autopsy series (parathyroid glands are not routinely examined) and due to reporting bias. Women were affected more commonly than men (5.8:1; 99 vs. 17, respectively), with a mean age at presentation of 58.5 years, when reported. The most common primary sites of malignancies that metastasized to the parathyroid glands were breast carcinomas (66.9%, n = 85), melanoma (11.8%, n = 15), and lung carcinoma (5.5%, n = 7), with carcinomas representing 86.6% of metastases. Metastases were nearly always identified as part of widely metastatic disease, with only five (3.2%) cases reported as isolated metastases. Tumor-to-tumor metastases comprised 5.5% of all metastases to the parathyroid glands (metastases to parathyroid adenoma). A significant clinical finding of metastases to the parathyroid glands was the development of deranged calcium homeostasis, well beyond the 9 (7.2%) cases with primary parathyroid gland disease present. Although concurrent conditions (renal disease; bone metastases) may partially affect calcium metabolism, the onset of calcium derangement seemed to coincide with parathyroid gland metastases and not systemic disease. In summary, metastases to the parathyroid glands are uncommon, potentially under-recognized in patients who have otherwise widely metastatic tumors. Women are affected more often than men, with breast carcinomas (66.9%) and melanoma (11.8%) the most common primary tumors. Calcium homeostasis is affected, probably as a result of parathyroid gland parenchymal destruction.
PubMed ID: 28875280
Article Size: 1 MB

Ectopic Hamartomatous Thymoma: A Review Of The Literature With Report Of New Cases And Proposal Of A New Name: Biphenotypic Branchioma.

Sato K, Thompson LDR, Miyai K, Kono T, Tsuda H.
Head Neck Pathol. 2017 Sep 6. [Epub ahead of print]
Ectopic hamartomatous thymoma (EHT) is a rare benign neoplasm of the lower neck suggesting branchial origin. Despite use of the term thymoma in the nomenclature, there is no evidence of thymic origin or differentiation. It affects middle-aged adults with a remarkable male predominance. To date less than 80 cases have been reported in the English literature. We present here two additional cases of EHT. The first is a benign case in a 31-year-old man, showing typical histological features. The second is a malignant case in a 70-year-old woman, showing intraductal carcinoma arising in intimate association with an EHT. These cases are presented in the context of a review of cases reported in the English literature. The exact origin has not been identified, but is considered to be of branchial apparatus, creating a quandary about the best terminology. Recently, the designation “branchial anlage mixed tumor” or “thymic anlage tumor” were proposed, but do not quite reflect the true nature of the neoplasm. To avoid taxonomic confusion, international consensus on terminology is desired. As this entity is a neoplasm that shows dual mesoderm and endoderm derivation/differentiation, we propose a new name “biphenotypic branchioma.”
PubMed ID: 28879635
Article Size: 2 MB

Lobular capillary hemangioma (pyogenic granuloma) of the oral cavity.

Thompson LD.
Ear Nose Throat J. 2017 Jul;96(7):240.
FIRST PARAGRAPH: Lobular capillary hemangioma (LCH), sometimes also called pyogenic granuloma or epulis gravidarum, is a benign overgrowth of capillaries showing a vascular phenotype. There are several etiologic factors, including hormones (increased in pregnancy and in patients using oral contraceptives), localized trauma (biting, fractured tooth, poor restorations), and when there is poor oral hygiene.
PubMed ID: 28719705
Article Size: <1 MB

Non-Neoplastic Diseases of the Head and Neck, (1st series, Vol. 11)

AFIP Atlas of Nontumor Pathology: Non-Neoplastic Diseases of the Head and Neck

Bruce M. Wenig, MD • Esther L. B. Childers, MD • Mary S. Richardson, MD • Raja R. Seethala, MD • Lester D.R. Thompson, MD


  • Hardcover: 491 pages
  • Publisher: ARP Press; 1st edition (2017)
  • Language: English
  • ISBN-10: 1-9334-77-37-7
  • ISBN-13: 978-1-933477-37-4
  • Product Dimensions: approx. 8.75 x 1.125 x 11 inches

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Nasopharyngeal Angiofibroma: A Clinical, Histopathological and Immunohistochemical Study of 42 Cases with Emphasis on Stromal Features.

Sánchez-Romero C, Carlos R, Díaz Molina JP, Thompson LDR, de Almeida OP, Rumayor Piña A.
Head Neck Pathol. 2017 May 15. [Epub ahead of print]
Nasopharyngeal angiofibroma is a benign but aggressive tumor of unknown etiology, typically occurring in adolescent males. It is described as a rare neoplasm; however, the prevalence seems to have geographic differences. All cases referred to our head and neck clinical and pathology service were reviewed. Most of the patients presented at an advanced stage. The clinical and radiographic features are presented and discussed. Histologically, the tumor shows a highly vascular fibrous proliferation with characteristic plump, angulated and stellate cells, categorized as fibroblasts. Immunohistochemistry was performed on 42 cases to further elucidate the nature of these cells. The stromal cells expressed vimentin and factor XIIIa, the latter expressed most commonly in the giant stellate cells. Inflammation was almost exclusively present in peripheral subepithelial areas. Mast cells were abundant, even in the absence of other inflammatory cells. Lymphatics were observed principally in peripheral regions. Proliferating cells (Ki-67 reactive) were restricted to endothelial cells.
PubMed ID: 28508272
Article Size: 3 MB


Thompson LD.
Ear Nose Throat J. 2017 Apr-May;96(4-5):160.
FIRST PARAGRAPH: Elastofibroma is an ill-defined fibroelastic tumor-like condition that affects the neck and upper shoulders. There is a genetic predisposition, with multifocality suggesting an enzymatic defect that results from abnormal elastogenesis. Patients usually present in the 60- to 70-year range, with females affected much more often than males (5:1). Although perhaps due to reporting bias, there is an increased incidence in Japanese patients.
PubMed ID: 28489232
Article Size: <1 MB

New tumor entities in the 4th edition of the World Health Organization classification of head and neck tumors: Nasal cavity, paranasal sinuses and skull base

Thompson LDR, Franchi A.
Virchows Arch. 2017 Apr 25. [Epub ahead of print]
TheWorld Health Organization recently published the 4th edition of the Classification of Head and Neck Tumors, including several new entities, emerging entities, and significant updates to the classification and characterization of tumor and tumor-like lesions, specifically as it relates to nasal cavity, paranasal sinuses, and skull base in this overview. Of note, three new entities (NUT carcinoma, seromucinous hamartoma, biphenotypic sinonasal sarcoma,) were added to this section, while emerging entities (SMARCB1-deficient carcinoma and HPV-related carcinoma with adenoid cystic-like features) and several tumor-like entities (respiratory epithelial adenomatoid hamartoma, chondromesenchymal hamartoma) were included as provisional diagnoses or discussed in the setting of the differential diagnosis. The sinonasal tract houses a significant diversity of entities, but interestingly, the total number of entities has been significantly reduced by excluding tumor types if they did not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. Refinements to nomenclature and criteria were provided to sinonasal papilloma, borderline soft tissue tumors, and neuroendocrine neoplasms. Overall, the new WHO classification reflects the state of current understanding for many relatively rare neoplasms, with this article highlighting the most significant changes.
PubMed ID: 28444451
Article Size: 6 MB

Neuroendocrine tumors of the larynx.

Thompson LD.
Ear Nose Throat J. 2016 Jul;95(7):262-6.
FIRST PARAGRAPH: Neuroendocrine neoplasms of the larynx encompass five separate tumors: paraganglioma, typical carcinoid, atypical carcinoid, small cell carcinoma, and large cell neuroendocrine carcinoma. Many synonyms are employed, with well-, moderately, and poorly differentiated neuroendocrine carcinoma commonly applied to the middle three tumors (World Health Organization preferred terminology). Paraganglioma is an exceedingly uncommon neuroendocrine tumor in the larynx, as is large cell neuroendocrine carcinoma, and therefore these will not be further discussed.
PubMed ID: 27434472
Article Size: <1 MB

Hailey-Hailey disease.

Thompson LD.
Ear Nose Throat J. 2016 Sep;95(9):370.
FIRST PARAGRAPH: Hailey-Hailey disease is a genodermatosis characterized by incomplete penetrance of an autosomal dominant disorder with defects in the ATP2C1 gene. Patients present with well-demarcated, erythematous plaques that often show crusting. The plaques may be vegetative, commonly associated with a distinct malodor. There may be associated burning or itching. While intertriginous areas are most commonly affected, the neck is also frequently involved. There is a natural remission and exacerbation cycle, with heat, moisture, and trauma the most common exacerbating factors. The lesions may be managed by corticosteroids or antibiotics, along with retinoids for severe disease.
PubMed ID: 27657314
Article Size: <1 MB

Secretory carcinoma.

Thompson LD.
Ear Nose Throat J. 2016 Dec;95(12):474-476.
FIRST PARAGRAPH: Secretory carcinoma, first described as mammary analogue secretory carcinoma (MASC), is a recently described, distinctive malignant salivary gland tumor that is quite similar to secretory breast carcinoma, defined by the t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK3 fusion product. The vast majority of these tumors used to be included in the acinic cell carcinoma category.
PubMed ID: 27929593
Article Size: <1 MB

Thyroglossal duct cyst.

Thompson LD.
Ear Nose Throat J. 2017 Feb;96(2):54-55.
FIRST PARAGRAPH: Embryologically, the thyroglossal duct develops as the thyroid anlage descends from the foramen cecum at the base of the tongue to its final resting point in the pretracheal inferior midline neck. The duct usually involutes, but persistence may give rise to a clinical cyst. Thyroglossal duct remnant cysts (TGDCs) are one of the most common neck lesions seen clinically, showing a bimodal age distribution in the first and fifth decades, and identified in approximately 2.2/100,000 population at risk each year. While there is an equal sex distribution, males tend to predominate in pediatric patients while females predominate among adults.
PubMed ID: 28231361
Article Size: <1 MB

Ossifying fibroma of the maxilla and sinonasal tract: Case series

Liu JJ, Thompson LD, Janisiewicz AM, Shibuya TY, Keschner DB, Garg R, Lee JT.
Allergy Rhinol (Providence). 2017 Mar 1;8(1):32-36. doi: 10.2500/ar.2017.8.0190
BACKGROUND: Head and neck ossifying fibroma (OF) is a rare, benign, locally aggressive, fibro-osseous tumor. The mandible is the most common site of involvement, followed by the maxilla, and, less frequently, the sinonasal cavities, orbit, skull base, and calvarium. In this study, we aimed to expand our understanding of this entity by presenting a case series of OF that involved the maxilla and sinonasal tract.
METHODS: A multicenter retrospective review was performed on all the patients with a diagnosis of OF from 2004 to 2013. Data were collected with respect to age, sex, clinical presentation, treatment, and outcome.
RESULTS: A total of 13 patients were identified. The mean age was 37 years, with a female predominance (69%). The maxillary sinus was most frequently involved site (46%). Eighty-five percent underwent open surgical resection. After a mean follow-up time of 47.3 months, three patients (23%) developed recurrent disease; all of whom were treated with an open approach.
CONCLUSION: Of the maxilla and sinonasal tract is an uncommon clinicopathologic entity. Although a timely diagnosis may obviate the need for external approaches, open surgical resection is often still necessary for management of extensive lesions. Close follow-up and additional surgery may also be required to treat recurrent disease.
PubMed ID: 28381325
Article Size: <1 MB

Thyroglossal Duct Cyst Carcinomas in Pediatric Patients: Report of Two Cases with a Comprehensive Literature Review

Thompson LD, Herrera HB, Lau SK.
Head Neck Pathol. 2017 March 14. [Epub ahead of print]
Thyroglossal duct cyst (TGDC) carcinomas are rarely encountered in the pediatric population. The clinical behavior of these tumors in the pediatric setting is unclear and management is not well defined. Two cases of pediatric thyroglossal duct cyst carcinoma were identified in a review of all thyroglossal duct cysts diagnosed over a ten year period. These two cases were analyzed along with 57 cases of thyroglossal duct cyst carcinoma affecting patients less than 21 years of age compiled from the English literature. Fifty-nine patients (36 females, 23 males) aged 6–20 years (mean 15.0 years) were identified. All presented with an anterior midline neck mass, which was typically mobile and non-tender. The average tumor size was 2.6 cm. Histologically, all tumors were papillary thyroid carcinomas arising in a background of a thyroglossal duct cyst. The tumors exhibited a papillary, follicular, or mixed architecture with classical papillary thyroid carcinoma nuclear features. Soft tissue extension was present in 16 cases. All patients were managed surgically with a Sistrunk procedure, with additional thyroidectomy performed in 29 patients, combined with a lymph node dissection (n = 15), or a Sistrunk and lymph node dissection (n = 5). All patients were stage I at presentation, with 11 showing lymph node metastases. Postoperative radioactive iodine was employed in 20 patients. A papillary carcinoma of the thyroid gland was reported in four of the patients who had concurrent/subsequent thyroidectomies. Recurrences were reported in four patients, with distant metastases in one patient, who died of disease (13 months). Follow up data was available for 45 patients, with an overall mean follow-up of 54.5 months. All patients were alive, with the exception of one who died with disease. TGDC carcinomas in pediatric patients is associated with a good overall prognosis, best managed by Sistrunk procedure alone, with selected lymph node dissection if clinically indicated.
PubMed ID: 28293858
Article Size: 1.5 MB

Update From the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumours of the Ear.

Thompson LD.
Head Neck Pathol. 2017 Mar;11(1):78-87. doi: 10.1007/s12105-017-0790-5. Epub 2017 Feb 28.
The 2017 fourth edition of the World Health Organization Classification of Tumours, specifically as it relates to the ear (Chap. 9), has several changes. Importantly, the number of entities has been significantly reduced by omitting tumors or lesions if they do not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. These entities include: embryonal rhabdomyosarcoma, osteoma, exostosis, angiolymphoid hyperplasia with eosinophilia, Schneiderian papilloma, inverted papilloma, lipoma of the internal auditory canal, hemangioma, hematolymphoid tumors, and secondary tumors. Paraganglioma was included in the neck chapter. New entries include otosclerosis and cholesteatoma, while refinements to nomenclature, classification and criteria were incorporated into the ceruminous gland tumors and epithelial tumors of the middle and inner ear. Specifically, the middle and inner ear were combined, as practical limitations of origin and imaging make a definitive separation artificial. The classification reflects the state of current understanding for these uncommon entities, with this update only highlighting selected entities that were the most significantly changed.
PubMed ID: 28247225
Article Size: 4.6 MB

Laryngeal Dysplasia, Squamous Cell Carcinoma, and Variants

Thompson, LDR.
Surg Pathol Clin. 2017 Mar;10(1):15-33.
Squamous cell carcinoma (SCC) is a malignant epithelial tumor showing evidence of squamous differentiation. It is the most common malignancy of the larynx, with several variants (verrucous, exophytic or papillary, spindle-cell, basaloid, acantholytic, adenosquamous) recognized, with well-established precursor lesions. Dysplasia is now separated into only low-grade and high-grade categories. Each SCC variant has unique cytomorphologic features and histologic differential diagnoses that are important to consider, as management and outcomes are different.
PubMed ID: 28153131
Article Size: 13 MB

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

Thompson LD.
Mod Pathol. 2017 Jan;30(s1):S1-S26. doi: 10.1038/modpathol.2016.119.
One of the most challenging diagnostic categories within tumors of the sinonasal tract is the small round blue cell tumors. Biopsies are usually small and limited, resulting in considerable diagnostic difficulty for practicing surgical pathologists. These tumors share several overlapping histologic and immunophenotypic findings while also showing considerable variation within and between cases. Specific tumor site of origin, imaging findings, and clinical findings must be combined with the histology and pertinent ancillary studies if the correct diagnosis is to be reached. Discrimination between neoplasms is critical as there are significant differences in therapy and overall outcome. It is important to have a well developed differential diagnosis for this category of tumors, where each of the diagnoses is considered, evaluated, and either confirmed or excluded from further consideration. In an undifferentiated tumor, showing a small round blue cell morphology, using the mnemonic ‘MR SLEEP’ helps to highlight tumors to consider: melanoma, mesenchymal chondrosarcoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carcinoma), small cell osteosarcoma, lymphoma, esthesioneuroblastoma (olfactory neuroblastoma), Ewing sarcoma/primitive neuroectodermal tumor, pituitary adenoma, and plasmacytoma. A panel of pertinent immunohistochemistry studies, histochemistries and/or molecular tests should aid in reaching a diagnosis, especially when taking the pattern and intensity of reactions into consideration.
PubMed ID: 28060373
Article Size: 4 MB

Template for Reporting Results of Biomarker Testing of Specimens From Patients With Thyroid Carcinoma.

Chiosea S, Asa SL, Berman MA, Carty SE, Currence L, Hodak S, Nikiforov YE, Richardson MS, Seethala RR, Sholl LM, Thompson LD, Wenig BM, Worden F; Members of the Cancer Biomarker Reporting Committee, College of American Pathologists.
Arch Pathol Lab Med. 2016 Sep 28. [Epub ahead of print]
The College of American Pathologists offers these templates to assist pathologists in providing clinically useful and relevant information when reporting results of biomarker testing. The College regards the reporting elements in the templates as important elements of the biomarker test report, but the manner in which these elements are reported is at the discretion of each specific pathologist, taking into account clinician preferences, institutional policies, and individual practice.
The College developed these templates as educational tools to assist pathologists in the useful reporting of relevant information. It did not issue them for use in litigation, reimbursement, or other contexts. Nevertheless, the College recognizes that the templates might be used by hospitals, attorneys, payers, and others. The College cautions that use of the templates other than for their intended educational purpose may involve additional considerations that are beyond the scope of this document.
Completion of the template is the responsibility of the laboratory performing the biomarker testing and/or providing the interpretation. When both testing and interpretation are performed elsewhere (e.g., a reference laboratory), synoptic reporting of the results by the laboratory submitting the tissue for testing is also encouraged to ensure that all information is included in the patient’s medical record and thus readily available to the treating clinical team.
PubMed ID: 27681332
Article Size: 75 KB

Thyroglossal Duct Cyst Carcinomas: A Clinicopathologic Series of 22 Cases with Staging Recommendations

Thompson LD, Herrera HB, Lau SK.
Head Neck Pathol. 2016 Oct 4. [Epub ahead of print].
Carcinomas arising from thyroglossal duct remnant cysts (TGDCs) are rare, without well-defined management and staging criteria. All TGDCs (n = 685) diagnosed between 2005 and 2015 were retrospectively reviewed, with 22 carcinomas identified (3.2 % incidence). Twenty-two patients (17 females, 5 males), aged 12-64 years (mean 39.9 years; median 39 years) were identified. An anterior, superior midline neck mass was the presenting symptom in all patients. A cancer diagnosis [all papillary thyroid carcinoma (PTC)] was made after the Sistrunk procedure (SP), with a Bethesda Category V or VI classification preoperatively by fine needle aspiration in 5 of 12 cases tested. A SP was performed in all patients, with total thyroidectomy concurrently (n = 4) or subsequently (n = 12). A selected neck dissection was performed in 5 patients, with metastases found in 3. Of the patients who had a thyroidectomy, synchronous PTC was identified in 6 (thus, 6 of 22 patients had synchronous thyroid gland primaries). This supports an origin from extra-thyroidal remnants (cyst origin) rather than metastatic tumor from a thyroid gland primary. Follow-up radioactive iodine therapy was performed in 13 patients. Metastatic disease to local lymph nodes 57 months after presentation was seen in 1 patient, with all others alive and disease free (mean 3.8 years; range 0.4-10.8 years). The TGDCs ranged from 0.8 to 5 cm (mean 2.3 cm), while the PTCs ranged from 0.1 to 3.8 cm (mean 1.4 cm). All of the tumors were classical PTC, showing a sclerotic and infiltrative pattern, with a capsule present in 11. Lymphovascular invasion was detected in 11; margins were positive in 6. Using currently defined criteria, the patients were separated into AJCC stage group I (n = 21) or II (n = 1). However, if extension into the adipose tissue (n = 11), skeletal muscle (n = 10), or perineural/perivascular tissues (n = 10) were used to stage the patients, interpreted to represent the equivalent of “extrathyroidal extension” (n = 13) as defined for thyroid gland primaries, there would be 15 group I and 7 group III cases. All seven group III patients were ≥45 years. Three of four patients with lymph node metastasis also showed soft tissue extension. In conclusion, TGDC carcinomas (TGDCCa) are uncommon, with all classical PTC. For “microcarcinomas” (≤1 cm), conservative management can be used for patients <45 years (i.e., Sistrunk procedure only); for >1 cm tumors, and due to the high incidence of concurrent papillary carcinoma and higher stage at presentation in older patients, completion thyroidectomy is recommended for patients ≥45 years. Thus, even though a good prognosis can be expected for PTC developing in TGDCs, staging is advocated to more appropriately match therapeutic interventions.
PubMed ID: 27704385
Article Size: 2.5 MB

Myeloid sarcoma of the breast soft tissue following allogeneic bone marrow transplantation

Chou JL, Thompson LD.
J Case Rep Images Oncology 2016;2:71–73.
FIRST PARAGRAPH: A 47-year-old female presented with high-risk myelodysplastic syndrome (MDS) without detectable cytogenetic abnormality from the bone marrow specimen. Initially, she received azacytidine while awaiting bone marrow transplantation (BMT). After successful allogeneic BMT from a mismatched related donor, she received post-transplant care including management of transplant-related toxicity and skin manifestations of graft versus host disease (GVHD) in a designated BMT center. Subsequent bone marrow showed no evidence of MDS, and she is currently free from GVHD.
Article Size: <1 MB

Inter-Observer Variation in the Pathologic Identification of Extranodal Extension in Nodal Metastasis from Papillary Thyroid Carcinoma

Du E, Wenig BM, Su HK, Rowe ME, Haser GC, Asa SL, Baloch Z, Faquin WC, Fellegara G, Giordano T, Ghossein R, LiVolsi VA, Lloyd R, Mete O, Ozbek U, Rosai J, Suster S, Thompson LD, Turk AT, Urken ML.
Thyroid. 2016 Jun;26(6):816-9.
Background: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases.
Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE.
Results: The overall strength of agreement in identifying ENE was only fair (j = 0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997.
Conclusions: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists’ identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.
PubMed ID: 27089928
Article Size: <1 MB

Subsets of Salivary Duct Carcinoma Defined by Morphologic Evidence of Pleomorphic Adenoma, PLAG1 or HMGA2 Rearrangements, and Common Genetic Alterations

Chiosea SI, Thompson LD, Weinreb I, Bauman JE, Mahaffey AM, Miller C, Ferris RL, Gooding WE.
Cancer. 2016 Oct 15;122(20):3136-3144. doi: 10.1002/cncr.30179. Epub 2016 Jul 5.
BACKGROUND: The authors hypothesized that histogenetic classification of salivary duct carcinoma (SDC) could account for de novo tumors and those with morphologic or molecular evidence (pleomorphic adenoma gene 1 [PLAG1], high-mobility group AT hook 2 [HMGA2] rearrangement, amplification) of pleomorphic adenoma (PA).
METHODS: SDCs (n = 66) were reviewed for morphologic evidence of PA. PLAG1 and HMGA2 alterations were detected by fluorescence in situ hybridization (FISH). PLAG1-positive tumors were tested by FISH for fibroblast growth factor receptor 1 (FGFR1) rearrangement. Thirty-nine tumors were analyzed using a commercial panel for mutations and copy number variations in 50 cancer-related genes.
RESULTS: On the basis of combined morphologic and molecular evidence of PA, 4 subsets of SDC emerged: 1) carcinomas with morphologic evidence of PA but intact PLAG1 and HMGA2 (n = 22); 2) carcinomas with PLAG1 alteration (n = 18) or 3) HMGA2 alteration (n = 12); and 4) de novo carcinomas, without morphologic or molecular evidence of PA (n = 14). The median disease-free survival was 37 months (95% confidence interval, 28.4-45.6 months). Disease-free survival and other clinicopathologic parameters did not differ for the subsets defined above. Combined Harvey rat sarcoma viral oncogene homolog/phosphatidylinositol-4,5-biphosphate 3-kinase, catalytic subunit α (HRAS/PIK3CA) mutations were observed predominantly in de novo carcinomas (5 of 8 vs 2 of 31 tumors; P = .035). Erb-B2 receptor tyrosine kinase 2 (ERBB2) copy number gain was not observed in de novo carcinomas (0 of 8 vs 12 of 31 tumors; P = .08). Tumor protein 53 (TP53) mutations were more common in SDC ex pleomorphic adenomas than in de novo carcinomas (17 of 31 vs 1 of 8 tumors; P = .033).
CONCLUSIONS: The genetic profile of SDC varies with the absence or presence of pre-existing PA and its cytogenetic signature. Most de novo SDCs harbor combined HRAS/PIK3CA mutations and no ERBB2 amplification.
PubMed ID: 27379604
Article Size: <1 MB

Cervical Lymph Node Metastasis in Adenoid Cystic Carcinoma of the Larynx: A Collective International Review

Coca-Pelaz A, Barnes L, Rinaldo A, Cardesa A, Shah JP, Rodrigo JP,, Suárez C,, Eloy JA, Bishop JA, Devaney KO, Thompson LD, Wenig BM, Strojan P, Hamoir M, Bradley PJ,, Gnepp DR,, Silver CE, Slootweg PJ, Triantafyllou A, Vander Poorten V,, Williams MD, Skálová A, Hellquist H, Teymoortash A, Medina JE, Robbins KT, Pitman KT, Kowalski LP, de Bree R, Mendenhall WM, Takes RP, Ferlito A.
Adv Ther. 2016 Apr;33(4):553-79.
Adenoid cystic carcinoma (AdCC) of the head and neck is a well-recognized pathologic entity that rarely occurs in the larynx. Although the 5-year locoregional control rates are high, distant metastasis has a tendency to appear more than 5 years post treatment. Because AdCC of the larynx is uncommon, it is difficult to standardize a treatment protocol. One of the controversial points is the decision whether or not to perform an elective neck dissection on these patients. Because there is contradictory information about this issue, we have critically reviewed the literature from 1912 to 2015 on all reported cases of AdCC of the larynx in order to clarify this issue. During the most recent period of our review (1991-2015) with a more exact diagnosis of the tumor histology, 142 cases were observed of AdCC of the larynx, of which 91 patients had data pertaining to lymph node status. Eleven of the 91 patients (12.1%) had nodal metastasis and, based on this low proportion of patients, routine elective neck dissection is therefore not recommended.
PubMed ID: 27084720
Article Size: <1 MB

Update on follicular variant of papillary thyroid carcinoma with an emphasis on new terminology: noninvasive follicular thyroid neoplasm with papillary-like nuclear features

Thompson, LDR.
Diagnostic Histopathology 2016.
The most common papillary thyroid carcinoma (PTC) variant is the follicular variant, representing w30% of all PTCs. The tumour is most common in middle aged (4th e 5th decades) women, who usually present with a single dominant nodule (about 3 cm). By definition, follicular architecture must be the dominant finding, while demonstrating the nuclear features of PTC. Papillary structures are <1% of volume, while necrosis, increased mitoses (>3/10 high power fields) and psammoma bodies are absent. The tumour category is divided into “encapsulated/well demarcated” and “invasive” types. The nuclear features include enlarged, elongated and overlapping nuclei; membrane irregularities (irregular contours, grooves and pseudoinclusions); chromatin clearing, margination and glassy nuclei. When the tumour is encapsulated/well demarcated without invasion, demonstrating the other inclusion and exclusion criteria, the new name of “Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features” (NIFTP) is used, a tumour that requires no additional treatment.
Article Size: 8.4 MB

A Clinicopathologic Series of 685 Thyroglossal Duct Remnant Cysts

Thompson LD, Herrera HB, Lau SK.
Head Neck Pathol. 2016 May 9. [Epub ahead of print]
The clinical features of thyroglossal duct remnant cysts (TGDC) have been well described, however the histopathologic aspects of these lesions have not been addressed in a detailed manner. In particular, there has been no large community practice based series evaluating TGDC histologically compared with management outcomes. A retrospective review of all TGDC diagnosed between 2005 and 2015 was performed. Six hundred eighty-five patients were identified (344 males; 341 females). Age at presentation was bimodal (first and fifth decades) and ranged from 0.8 to 87 years (mean 31.3 years). Males predominate in children (150:111); females in adults (230:194). Patients presented most frequently with a mobile midline neck mass in an infrahyoid location. An associated skin fistula (n = 67) was twice as common in pediatric as adult patients. The average cyst size was 2.4 cm (range 0.4-9.9 cm) by imaging studies and 2.6 cm (range 0.2-8.5 cm) by pathologic examination; pediatric patients had smaller cysts (mean 2.1 cm) than adults (mean 2.8 cm). Histologically, 257 (38 %) TGDC were lined by respiratory epithelium alone, 68 (10 %) squamous epithelium alone, 347 (51 %) exhibited both respiratory and squamous epithelium, and 13 (1 %) had no identifiable epithelial lining. Four hundred eighty-four (71 %) TGDC had associated thyroid gland tissue present within the cyst wall (n = 282), skeletal muscle (n = 71), adipose tissue (n = 34), or a combination of these sites (n = 97). The hyoid bone was identified in 647 (grossly and/or histologically), and absent in 38. Surgical management consisted of Sistrunk procedure (n = 647), cystectomy (n = 31), or thyroidectomy/thyroid lobectomy (n = 7). Treatment related complications were observed in 6 patients, which included vocal cord damage, seroma, and hematoma. Recurrences developed in 20 (3 %) patients, 14 of whom were managed initially by cystectomy. Papillary thyroid carcinoma was identified in 22 (3.2 %) TGDC. In summary, TGDC show a bimodal peak in the 1st and 5th decades, commonly presenting as a midline cervical lesion below the hyoid bone, associated with a skin fistula in 10 %. Histologically TGDC are most commonly lined by a combination of respiratory and squamous epithelium. Thyroid gland tissue is identified in 71 % of cases (0.45 cm mean size), although not limited to the cyst wall, but present in the surrounding soft tissues. Rare TGDC may harbor malignancy (3.2 %). TGDC are most effectively managed by Sistrunk procedure rather than excision, which carries low rates of complications (1 %) and recurrence (3 %).
PubMed ID: 27161104
Article Size: 2.7 MB

Ear and temporal bone meningioma

Thompson, LD.
Ear Nose Throat J. 2016 Apr-May;95(4-5):146.
FIRST PARAGRAPH: Meningiomas account for 30% of all intracranial neoplasms, but primary extracranial (ectopic) meningiomas of the ear and temporal bone are less common, accounting for about 10% of all ear and temporal bone tumors. Meningiomas are derived from the arachnoid cap cells, also called pacchionian bodies.
PubMed ID: 27140011
Article Size: <1 MB

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

Thompson, LD.
Mod Pathol. 2016 Jul;29(7):698-707.
Encapsulated follicular variant of papillary thyroid carcinoma is a common thyroid gland cancer, with a highly indolent behavior. Recently, reclassification as a non-malignant neoplasm has been proposed. There is no comprehensive, community hospital based longitudinal evaluation of encapsulated follicular variant of papillary thyroid carcinoma. Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma were identified in a review of all thyroid gland surgeries performed in 2002 within the Southern California Permanente Medical Group. All histology slides were reviewed and follow-up obtained. Seventy-five women and nineteen men, aged 20-80 years (mean 45.6 years), had a single (n=61), multiple (same lobe; n=20), or bilateral (n=13) tumor(s), ranging in size from 0.7 to 9.5 cm in diameter (mean 3.3 cm). Histologically, all cases demonstrated a well-formed tumor capsule, with capsular and/or lymphovascular invasion in 17 and no invasion in 77 cases. Lymph node metastases were not identified. The tumors had a follicular architecture, without necrosis or 43 mitoses/10 high-power fields (HPFs). Classical papillary thyroid carcinoma nuclear features were seen in at least three HPFs per 3mm of tumor diameter, including enlarged, elongated, crowded, and overlapping nuclei, irregular nuclear contours, nuclear grooves, and nuclear chromatin clearing. Lobectomy alone (n=41), thyroidectomy alone (n=34), or completion thyroidectomy (n=19) was the initial treatment combined with post-op radioablative iodine in 25 patients. All patients were without evidence of disease after a median follow-up of 11.8 years. Encapsulated follicular variant of papillary thyroid carcinoma showed benign behavior, supporting conservative surgery alone and reclassification of these tumors to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP).
PubMed ID: 27102347
Article Size: <1 MB

Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.

Nikiforov YE, Seethala RR, Tallini G, Baloch ZW, Basolo F, Thompson LD, Barletta JA, Wenig BM, Al Ghuzlan A, Kakudo K, Giordano TJ, Alves VA, Khanafshar E, Asa SL, El-Naggar AK, Gooding WE, Hodak SP, Lloyd RV, Maytal G, Mete O, Nikiforova MN, Nosé V, Papotti M, Poller DN, Sadow PM, Tischler AS, Tuttle RM, Wall KB, LiVolsi VA, Randolph GW, Ghossein RA.
JAMA Oncol. 2016 Aug 1;2(8):1023-9.
IMPORTANCE: Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.
OBJECTIVE: To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
DESIGN, SETTING, AND PARTICIPANTS: International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
MAIN OUTCOMES AND MEASURES: Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
RESULTS: Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.
CONCLUSIONS AND RELEVANCE: Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
PubMed ID: 27078145

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma.

Su HK, Wenig BM, Haser GC, Rowe ME, Asa SL, Baloch Z, Du E, Faquin WC, Fellegara G, Giordano T, Ghossein R, LiVolsi VA, Lloyd R, Mete O, Ozbek U, Rosai J, Suster S, Thompson LD, Turk AT, Urken ML.
Thyroid. 2016 Apr;26(4):512-7.
BACKGROUND: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases.
METHODS: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE.
RESULTS: The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE.
CONCLUSIONS: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists’ interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.
PubMed ID: 26953223
Article Size: <1 MB


Thompson LD.
Ear Nose Throat J. 2016 Mar;95(3):101..
FIRST PARAGRAPH: Rhinosporidium seeberi is the etiologic agent of a chronic, and usually painless, localized granulomatous infection of the mucous membranes of the sinonasal tract, conjunctiva, and urethra. Endemic in India and Sri Lanka, the disease is becoming more significant as a result of migration. R seeberi has not been definitively cultured but is thought to be a blue-green algae, with the infectious agent being a thick-walled sporangium containing endospores. It is passed to humans from animals (cats, free-grazing horses) or possibly fomites, identified in water or soil contaminated by waste.
PubMed ID: 26991216
Article Size: <1 MB

Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review.

Hellquist H, Skálová A, Barnes L, Cardesa A, Thompson LD, Triantafyllou A, Williams MD, Devaney KO, Gnepp DR,, Bishop JA, Wenig BM, Suárez C,, Rodrigo JP,, Coca-Pelaz A, Strojan P, Shah JP, Hamoir M, Bradley PJ,, Silver CE, Slootweg PJ, Vander Poorten V,, Teymoortash A, Medina JE, Robbins KT, Pitman KT, Kowalski LP, de Bree R, Mendenhall WM, Eloy JA, Takes RP, Rinaldo A, Ferlito A.
Adv Ther. 2016 Feb 19. [Epub ahead of print].
Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.
PubMed ID: 26895332
Article Size: 3 MB

Cervical lymph node metastasis in adenoid cystic carcinoma of oral cavity and oropharynx: A collective international review

Suárez C, Barnes L, Silver CE, Rodrigo JP , Shah JP, Triantafyllou A, Rinaldo A, Cardesa A, Pitman KT, Kowalski LP, Robbins KT , Hellquist H, Medina JE, de Bree R, Takes RP, Coca-Pelaz A , Bradley PJ, Gnepp DR, Teymoortash A, Strojan P, Mendenhall WM, Anderson Eloy J, Bishop JA, Devaney KO, Thompson LDR, Hamoir M, Slootweg PJ, Vander Poorten VV, Williams MD, Wenig BM, Skálová A, Ferlito A.
Auris Nasus Larynx. 2016 Oct;43(5):477-484.
The purpose of this study was to suggest general guidelines in the management of the N0 neck of oral cavity and oropharyngeal adenoid cystic carcinoma (AdCC) in order to improve the survival of these patients and/or reduce the risk of neck recurrences. The incidence of cervical node metastasis at diagnosis of head and neck AdCC is variable, and ranges between 3% and 16%. Metastasis to the cervical lymph nodes of intraoral and oropharyngeal AdCC varies from 2% to 43%, with the lower rates pertaining to palatal AdCC and the higher rates to base of the tongue. Neck node recurrence may happen after treatment in 0–14% of AdCC, is highly dependent on the extent of the treatment and is very rare in patients who have been treated with therapeutic or elective neck dissections, or elective neck irradiation. Lymph node involvement with or without extracapsular extension in AdCC has been shown in most reports to be independently associated with decreased overall and cause-specific survival, probably because lymph node involvement is a risk factor for subsequent distant metastasis. The overall rate of occult neck metastasis in patients with head and neck AdCC ranges from 15% to 44%, but occult neck metastasis from oral cavity and/or oropharynx seems to occur more frequently than from other locations, such as the sinonasal tract and major salivary glands. Nevertheless, the benefit of elective neck dissection (END) in AdCC is not comparable to that of squamous cell carcinoma, because the main cause of failure is not related to neck or local recurrence, but rather, to distant failure. Therefore, END should be considered in patients with a cN0 neck with AdCC in some high risk oral and oropharyngeal locations when postoperative RT is not planned, or the rare AdCC-high grade transformation.
PubMed ID: 27017314
Article Size: <1 MB

Diffuse hyperplasia of thyroid gland (Graves’ disease)

Thompson LDR.
Ear Nose Throat J. 2007 Nov;86(11):666-7.
FIRST PARAGRAPH: Widely known by its eponym Graves’ disease, diffuse hyperplasia of the thyroid gland is an autoimmune condition in which excess thyroid hormone production is unchecked by the normal feedback loop between the thyroid and the pituitary gland. The immune-system abnormality is mediated by antibodies to the thyrotropin receptor found on follicular epithelial cells. When the most specific antibody, known as thyroid-stimulating immunoglobulin (TSI), is bound to the thyrotropin receptor, the TSI mimics the action of pituitary thyrotropin and stimulates the follicular epithelium to produce hormone. The clinical effect of this autoimmune process is (1) thyrotoxicosis accompanied by diffuse thyroid enlargement and an infiltrative ophthalmopathy and (2) a spectrum of the systemic effects of excessive thyroid hormone production.
PubMed ID: 18225623
Article Size: <1 MB

Chondrodermatitis nodularis helicis.

Thompson LDR.
Ear Nose Throat J. 2007 Dec;86(12):734-5.
FIRST PARAGRAPH: Chondrodermatitis nodularis helicis (CDNH) is a non-neoplastic inflammatory and degenerative process of the external ear. It is characterized by necrobiotic changes in the dermis that extend down to the perichondrium; associated alterations are seen in the cartilaginous plate. The dermal injury is thought to be attributable to a combination of factors: local trauma, actinic damage, and the relatively tenuous vascularity of the auricle. The necrobiotic dermal collagen—and in some cases the cartilaginous matrix—is extruded through a crater-like defect in the epidermis; thus, CDNH is considered to be one of the transepidermal elimination disorders.
PubMed ID: 18217375
Article Size: <1 MB

Oral Traumatic Ulcer.

Thompson LD.
Ear Nose Throat J. 2011 Nov; 90(11):518-34.
FIRST PARAGRAPH: A traumatic ulcer is a chronic traumatic ulceration of the oral mucosa that shows unique histopathologic features. Also known as traumatic granuloma, eosinophilic granuloma, and Riga-Fede disease, this lesion is usually caused by some sort of mechanical injury. The most common causes include accidental trauma from biting, malposed teeth, and even sharp foodstuffs. However, self inflicted wounds caused by nocturnal clenching or tongue and lip biting, electrical and thermal injuries, hot foods or beverages, and even factitial injuries yield a similar finding. Ulceration of the ventral tongue as a result of tongue thrusting in infants with natal or neonatal teeth is referred to as Riga-Fede disease.
PubMed ID: 22109918
Article Size: <1 MB

Hotspot activating PRKD1 somatic mutations in polymorphous low-grade adenocarcinomas of the salivary glands

Weinreb I, Piscuoglio S, Martelotto LG, Waggott D, Ng CK, Perez-Ordonez B, Harding NJ, Alfaro J, Chu KC, Viale A, Fusco N, da Cruz Paula A, Marchio C, Sakr RA, Lim R, Thompson LD, Chiosea SI, Seethala RR, Skalova A, Stelow EB, Fonseca I, Assaad A, How C, Wang J, de Borja R, Chan-Seng-Yue M, Howlett CJ, Nichols AC, Wen YH, Katabi N, Buchner N, Mullen L, Kislinger T, Wouters BG, Liu FF, Norton L, McPherson JD, Rubin BP, Clarke BA, Weigelt B, Boutros PC, Reis-Filho JS.
Nat Genet. 2014;Nov;(46(11):1166-9.
Polymorphous low-grade adenocarcinoma (PLGA) is the second most frequent type of malignant tumor of the minor salivary glands. We identified PRKD1 hotspot mutations encoding p.Glu710Asp in 72.9% of PLGAs but not in other salivary gland tumors. Functional studies demonstrated that this kinase-activating alteration likely constitutes a driver of PLGA.
PubMed ID: 25240283
Article Size: 1 MB

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control

Maxwell JH, Thompson LD, Brandwein-Gensler MS, Weiss BG, Canis M, Purgina B, Prabhu AV, Lai C, Shuai Y, Carroll WR, Morlandt A, Duvvuri U, Kim S, Johnson JT, Ferris RL, Seethala R, Chiosea S.
JAMA Otolaryngol Head Neck Surg. 2015 Dec 1;141(12):1104-10.
IMPORTANCE: Positive margins are associated with poor prognosis among patients with oral tongue squamous cell carcinoma (SCC). However, wide variation exists in the margin sampling technique.
OBJECTIVE: To determine the effect of the margin sampling technique on local recurrence (LR) in patients with stage I or II oral tongue SCC.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective study was conducted from January 1, 1986, to December 31, 2012, in 5 tertiary care centers following tumor resection and elective neck dissection in 280 patients with pathologic (p)T1-2 pN0 oral tongue SCC. Analysis was conducted from June 1, 2013, to January 20, 2015.
INTERVENTIONS: In group 1 (n = 119), tumor bed margins were not sampled. In group 2 (n = 61), margins were examined from the glossectomy specimen, found to be positive or suboptimal, and revised with additional tumor bed margins. In group 3 (n = 100), margins were primarily sampled from the tumor bed without preceding examination of the glossectomy specimen. The margin status (both as a binary [positive vs negative] and continuous [distance to the margin in millimeters] variable) and other clinicopathologic parameters were compared across the 3 groups and correlated with LR.
RESULTS: Age, sex, pT stage, lymphovascular or perineural invasion, and adjuvant radiation treatment were similar across the 3 groups. The probability of LR-free survival at 3 years was 0.9 and 0.8 in groups 1 and 3, respectively (P = .03). The frequency of positive glossectomy margins was lowest in group 1 (9 of 117 [7.7%]) compared with groups 2 and 3 (28 of 61 [45.9%] and 23 of 95 [24.2%], respectively) (P < .001). Even after excluding cases with positive margins, the median distance to the closest margin was significantly narrower in group 3 (2 mm) compared with group 1 (3 mm) (P = .008). The status (positive vs negative) of margins obtained from the glossectomy specimen correlated with LR (P = .007), while the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin.
CONCLUSIONS AND RELEVANCE: The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.
PubMed ID: 26225798
Article Size: <1 MB

Update on Select Benign Mesenchymal and Meningothelial Sinonasal Tract Lesions

Thompson LD, Fanburg-Smith JC.
Head Neck Pathol. 2016 Mar;10(1):95-108.
Several benign and malignant mesenchymal and meningothelial lesions may preferentially affect or extend into the sinonasal tract. Glomangiopericytoma (GPC, formerly sinonasal-type hemangiopericytoma) is a specific tumor with a predilection to the sinonasal tract. Sinonasal tract polyps with stromal atypia (antrochoanal polyp) demonstrate unique histologic findings in the sinonasal tract. Juvenile nasopharyngeal angiofibroma (JNA) arises from specialized tissue in this location. Meningioma may develop as direct extension from its intracranial counterpart or as an ectopic tumor. Selected benign mesenchymal tumors may arise in the sinonasal tract and pose a unique differential diagnostic consideration, such as solitary fibrous tumor and GPC or lobular capillary hemangioma and JNA. Although benign and malignant vascular, fibrous, fatty, skeletal muscle, and nerve sheath tumors may occur in this location, this paper focuses on a highly select group of rare benign sinonasal tract tumors with their clinicopathological and molecular findings, and differential diagnosis.
PubMed ID: 26830398
Article Size: 4 MB

2016 SCPMG Thyroid NIFTP

Instructions for Validation of criteria for the new entity: Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP)

  1. Review these instructions and reply that you will be able to participate in the study in the time frame recommended
  2. Study the PowerPoint presentation, highlighting the features and criteria for the diagnosis
  3. Before beginning your review, ask Lester any questions, clarifications or concepts you may not clearly understand
  4. Please try to review the 30 cases in one or two seatings
  5. It will take about 30 minutes to look at the images, make a decision, and complete the appropriate line on the form
  6. The score you place (entry of 0 or 1) will be automatically added to create the 4th column
  7. Please provide your demographic data, which is only for Lester to use to avoid duplication, but also to allow the statistician to compare based on experience and volume of work
  8. Be able to complete this assignment before February 5, 2016. Return your completed Excel spreadsheet (see second tab of xls file; download below)
  9. Return Excel spreadsheet by email to
  10. Aggregated results and comparison to the 26 endocrine pathologists will be provided as soon as the statistical evaluation is complete
  11. Data will be combined with academic pathologists from England (18-20 people), Japanese practicing pathologists (about 25), and the consensus conference group
  12. The information will be used to “validate” the criteria for reproducibility both between practicing pathologists and experts, but also against pathologists trained in different countries
Download Size: 12.4 MB
Download Size: 4.7 MB
Download Size: 23 KB Excel file

Pleomorphic sarcoma of the neck.

Thompson LD.
Ear Nose Throat J. 2015 Sep;94(9):376-7.
Pleomorphic sarcoma is an uncommon neoplasm in the head and neck now that refinements in diagnostic techniques have more accurately classified tumors that used to be placed in this category.

FIRST PARAGRAPH: ‘Pleomorphic sarcoma’ is the World Health Organization’s preferred term for malignant fibrous histiocytoma. This high-grade pleomorphic malignant mesenchymal neoplasm is a diagnosis of exclusion after other sarcomas and pleomorphic neoplasms have been excluded by histochemistry, immunohistochemistry, electron microscopy, and/or molecular evaluation. Most of these tumors arise de novo, but postradiation tumors are not uncommon. To be considered as a postradiation tumor, the tumor must be located in the radiation field and it must develop at least 3 years after radiation in an area that was free of tumor before radiation.

PubMed ID: 26401667
Article Size: <1 MB

Angiolymphoid hyperplasia with eosinophilia.

Thompson LD.
Ear Nose Throat J. 2015 Oct-Nov;94(10-11):443-4.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular tumor that features immature blood vessels lined by epithelioid endothelial cells with a prominent inflammatory infiltrate, frequently showing a conspicuous eosinophil component.

FIRST PARAGRAPH: Angiolymphoid hyperplasia with eosinophilia (ALHE), sometimes called epithelioid hemangioma, is a benign vascular tumor. It features immature blood vessels lined by epithelioid endothelial cells with a prominent inflammatory infiltrate, frequently showing a conspicuous eosinophil component. There is controversy about whether this lesion is a reactive or benign neoplastic condition.

PubMed ID: 26535818
Article Size: <1 MB