Bruce M. Wenig

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

IMPORTANCEnAlthough 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.nnnOBJECTIVEnTo evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.nnnDESIGN, SETTING, AND PARTICIPANTSnInternational, 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.nnnMAIN OUTCOMES AND MEASURESnFrequency 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.nnnRESULTSnConsensus 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.nnnCONCLUSIONS AND RELEVANCEnThyroid 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.

Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma

The histopathologic diagnosis of follicular variant of papillary thyroid carcinoma (FVPCA) can be difficult. Recent reports have suggested that this neoplasm may be frequently overdiagnosed by pathologists. We examined the observer variation in the diagnosis of FVPCA in 87 tumors by 10 experienced thyroid pathologists. The criteria that the reviewers considered most helpful for making a diagnosis of FVPCA were also assessed. A concordant diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 39%. In this series, 24.1% of the patients had metastatic disease (n = 21). In the cases with metastatic disease, a diagnosis of FVPCA was made by all 10 reviewers with a cumulative frequency of 66.7%, and 7 of the reviewers made a diagnosis of FVPCA with a cumulative frequency of 100%. The most important criteria used to diagnose FVPCA included the presence of cytoplasmic invaginations into the nucleus (pseudo-inclusions), abundant nuclear grooves, and ground glass nuclei. These results suggest that although the diagnosis of FVPCA is variable even among experienced thyroid pathologists, most reviewers agreed on this diagnosis for patients with metastatic disease. The use of well-defined histopathologic features should improve the consistency in diagnosing FVPCA. Since most cases with metastatic disease had obvious invasion, caution should be used in making a diagnosis of FVPCA in the absence of the major histopathologic features or clear-cut invasive growth.

Respiratory Epithelial Adenomatoid Hamartomas of the Sinonasal Tract and Nasopharynx: A Clinicopathologic Study of 31 Cases

We report the clinicopathologic features of 31 cases of respiratory epithelial adenomatoid hamartomas occurring in the nasal cavity, paranasal sinuses, and nasopharynx. The patients included 27 men and 4 women ranging in age from 27 to 81 years (median, 58 years). Symptoms included nasal obstruction, nasal stuffiness, deviated septum, epistaxis, and chronic (recurrent) rhinosinusitis. The symptoms occurred over various time periods from as short as a few months to up to 8 years in duration. Physical examination identified the presence of a polypoid mass lesion(s), most often identified in one or both nasal cavities (n = 22). Within the nasal cavity the most common site of occurrence was the nasal septum, particularly along its posterior aspect. Other areas within the nasal cavity were also involved, as were the ethmoid sinus, frontal sinus, and nasopharynx. The gross appearance of the mass lesions suggested a diagnosis of an inflammatory polyp, but because of subtle differences, including frequent occurrence along the nasal septum and a more indurated quality, these polyps were considered unusual for the typical inflammatory polyps. Histologically, these lesions were characterized by a prominent glandular proliferation lined by ciliated respiratory epithelium originating from the surface epithelium. The differential diagnosis of these adenomatoid hamartomas includes schneiderian papillomas of the inverted type and adenocarcinomas. Diagnostic misinterpretations may result in untoward surgical intervention. Limited but complete surgical resection was the treatment of choice, following which there were no instances of recurrent disease.

The significance of immunohistochemically demonstrated nodal micrometastases in patients with squamous cell carcinoma of the head and neck

Objectives/Hypothesis Patients with primary squamous cell carcinoma of the head and neck have a relatively high risk of occult lymph node metastases. Pathological demonstration of these metastases may be difficult, and the detection of such occult metastases may identify patients who are at an increased risk for early recurrence or reduced survival. Immunohistochemistry may be applied in the identification of occult metastases that may be missed on routine (H&E) histological examination. The aim of the study is to determine the prevalence and prognostic significance of immunohistochemically identified micrometastases in squamous cell carcinoma of the head and neck.

Identification, classification, treatment, and prognosis of laryngeal paraganglioma. Review of the literature and eight new cases.

This study details the clinicopathologic features of 62 cases of laryngeal paraganglioma (LP), including 54 acceptable cases identified in the literature (although clinical information is lacking on 7 of these) and 8 previously unpublished cases identified from the Registry of Otolaryngic-Endocrine Pathology at the Armed Forces Institute of Pathology. Demographic findings show that the overwhelming majority of cases affect women (41:14), mainly in the fourth to sixth decades of life (age range, 14 to 83 years; median, 44 years), with a prevalence in the supraglottic larynx. These neoplasms are treated by surgical resection and are benign. Despite the characteristic pathologic features associated with LP, it is sometimes confused with other neoplasms, particularly neuroendocrine carcinomas of the larynx, and this confusion leads to unfortunate designations such as malignant paraganglioma and metastasizing paraganglioma of the larynx. Judging from the cases reported in this study and those identified in the literature, we conclude that malignant biologic behavior associated with LP is extraordinarily rare (<2%). Because of the misdiagnoses of LP, the prognosis associated with this entity has been skewed to suggest that LP may behave aggressively. This has led to the inappropriate classification of LP among the malignant categories of laryngeal neuroendocrine neoplasms. The goal of this study is to detail the features diagnostic of LP and to discuss the appropriate treatment, prognosis, and classification of these neoplasms.

Undifferentiated Malignant Neoplasms of the Sinonasal Tract

CONTEXTnThe most commonly encountered malignant neoplasms of the sinonasal tract are the keratinizing and nonkeratinizing types of squamous cell carcinoma. However, this complex anatomic region may represent the site of aggressive, non-squamous cell epithelial and nonepithelial malignant neoplasms of varying histogenesis, which are grouped under the term undifferentiated malignant neoplasms. Frequently, these undifferentiated malignancies share clinical and light microscopic features, which makes differentiation of one from the other virtually impossible without the use of adjunct analyses (eg, immunohistochemistry, electron microscopy, or molecular biologic studies). These tumors often are clinically aggressive and usually fatal, despite all attempts at controlling disease. Nevertheless, differentiating these tumors has clinical import because advances in therapeutic intervention may increase survival with good quality of life, and in some instances may achieve a cure.nnnOBJECTIVEnTo compare and contrast the clinical, light microscopic, and immunohistochemical features of sinonasal undifferentiated malignant neoplasms.nnnDATA SOURCESnCase-derived material and literature review.nnnCONCLUSIONSnA variety of undifferentiated malignant neoplasms occur in the sinonasal tract with overlapping clinical and pathologic findings. In limited biopsy material, differentiation of these tumor types can be challenging. The pathologist plays a primary role in establishing the correct diagnosis, which often necessitates the use of adjunct studies that allow for differentiating among these neoplasms.

Schneiderian-Type Mucosal Papillomas of the Middle Ear and Mastoid

Five cases of schneiderian-type mucosal papillomas arising in the middle ear space are reported. The patients were all women, ranging in age from 19 to 57 years (median, 31 years). Clinical complaints — unilateral conductive hearing loss, pain, or otorrhea — ranged from those lasting several months to recurrent problems spanning 20 years. All of the patients had a history of chronic otitis media predating the development of the papillomas; none of the patients had a history of sinonasal or nasopharyngeal schneiderian-type papillomas. Clinically, three patients had intact tympanic membranes, while the other two patients had perforated tympanic membranes through which a bulging polypoid mass was identified. Radiographic studies showed opacification of the middle ear space without evidence of osseous destruction. The intraoperative findings were of polypoid lesions filling the middle ear space, including involvement of the eustachian tube orifice. Histologically, the tumors were identical to sinonasal schneiderian papillomas. Immunohistochemical evaluation for human papillomavirus was negative. Surgical excision is the treatment of choice. In four of the patients, recurrent tumor was identified, necessitating additional surgery. In only one patient did the initial surgery result in complete ablation of the tumor. All patients are alive and free of recurrent disease over periods ranging from 6 months to 120 months (median, 84 months).

Laryngeal Paraganglioma versus Atypical Carcinoid Tumor

Paraganglioma and atypical carcinoid tumor of the larynx are two neuroendocrine neoplasms that have often been confused in the past, and even in the present, in the literature. The clinicopathological profile of the two lesions is presented and the differential diagnosis is discussed. A correct diagnosis is of paramount importance, since treatment and prognosis depend on diagnostic accuracy and differ for the two lesions. Paraganglioma of the larynx is usually benign, whereas atypical carcinoid tumor is malignant and has an aggressive clinical course.

Morphology in Conjunction with Immunohistochemistry is Sufficient for the Diagnosis of Mammary Analogue Secretory Carcinoma

AbstractnThe recently described mammary analogue secretory carcinoma (MASC) is a low-grade salivary gland malignancy that harbors the recurrent cytogenetic abnormality t(12;15) (p13;q25) ETV6-NTRK3. Confirmation of this is currently considered the gold standard for diagnosis. Some have postulated that morphology together with supporting immunohistochemistry is sufficient to diagnose MASC. In this study we retrospectively review a series of 19 MASCs diagnosed based on histology in conjunction with immunohistochemistry; subsequently we performed in situ hybridization using an ETV6 break-apart probe. Immunohistochemistry for S100 protein and mammaglobin as well as fluorescence in situ hybridization using the Vysis ETV6 Dual Color Break-Apart FISH Probe Kit were performed on all cases. The 19 cases were from 12 females and 7 males with ages ranging from 16 to 76xa0years (meanxa0=xa045xa0years). Sixteen cases were from the parotid gland, 1 case was from a periparotid lymph node and 2 cases were from the submandibular gland. All 19 cases demonstrated moderate to strong expression of S100 protein. Eighteen cases demonstrated strong, diffuse expression of mammaglobin, while one case had only rare tumor cells that strongly expressed mammaglobin. Eighteen of 19 cases (95xa0%) demonstrated the ETV6 rearrangement by fluorescence in situ hybridization. Given that morphology together with immunohistochemistry is highly correlated with the ETV6 gene rearrangement, we conclude that molecular confirmation is not required to diagnose MASC.

Neuroendocrine neoplasms of the sinonasal region

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small‐cell and large‐cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high‐grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined.