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.

No comprehensive series has evaluated the histologic features of pheochromocytoma to separate benign from malignant pheochromocytoma by histomorphologic parameters only. Fifty histologically malignant and 50 histologically benign pheochromocytomas of the adrenal gland were retrieved from the files of the Armed Forces Institute of Pathology. The patients included 43 females and 57 males, with an age range of 3-81 years (mean 46.7 years). Patients usually experienced hypertension (n = 79 patients). The mean tumor size was 7.2 cm (weight was 222 g). Histologically, the cases of malignant pheochromocytomas of the adrenal gland more frequently demonstrated invasion (vascular [score = 1], capsular [score = 1], periadrenal adipose tissue [score = 2]), large nests or diffuse growth (score = 2), focal or confluent necrosis (score = 2), high cellularity (score = 2), tumor cell spindling (score = 2), cellular monotony (score = 2), increased mitotic figures (>3/10 high power fields; score = 2), atypical mitotic figures (score = 2), profound nuclear pleomorphism (score = 1), and hyperchromasia (score = 1) than the benign tumors. A Pheochromocytoma of the Adrenal gland Scaled Score (PASS) weighted for these specific histologic features can be used to separate tumors with a potential for a biologically aggressive behavior (PASS > or =4) from tumors that behave in a benign fashion (PASS <4). The pathologic features that are incorporated into the PASS correctly identified tumors with a more aggressive biologic behavior. Application of these criteria to a large cohort of cases will help to elucidate the accuracy of this grading system in clinical practice.

Primary sinonasal tract mucosal malignant melanomas are uncommon tumors that are frequently misclassified, resulting in inappropriate clinical management. A total of 115 cases of sinonasal tract mucosal malignant melanoma included 59 females and 56 males, 13-93 years of age (mean 64.3 years). Patients presented most frequently with epistaxis (n = 52), mass (n = 42), and/or nasal obstruction (n = 34) present for a mean of 8.2 months. The majority of tumors involved the nasal cavity (n = 34), septum alone, or a combination of the nasal cavity and sinuses (n = 39) with a mean size of 2.4 cm. Histologically, the tumors were composed of a variety of cell types (epithelioid, spindled, undifferentiated), frequently arranged in a peritheliomatous distribution (n = 39). Immunohistochemical studies confirmed the diagnosis of sinonasal tract mucosal malignant melanomas with positive reactions for S-100 protein, tyrosinase, HMB-45, melan A, and microphthalmia transcription factor. Sinonasal tract mucosal malignant melanomas need to be considered in the differential diagnosis of most sinonasal malignancies, particularly carcinoma, lymphoma, sarcoma, and olfactory neuroblastoma. Surgery accompanied by radiation and/or chemotherapy was generally used. The majority of patients developed a recurrence (n = 79), with 75 patients dying with disseminated disease (mean 2.3 years), whereas 40 patients are either alive or had died of unrelated causes (mean 13.9 years). A TNM-type classification separated by anatomic site of involvement and metastatic disease is proposed to predict biologic behavior.

Over the past decade working as a co nsultant head and neck pathologist, I have come to rea lize the importance of nomencl ature and terminology in the diagnosis ofhead and neck organ diseases.Th ere have been many cases in which the pathologist has had the right diagnosis but has used a term that is unfam iliar to the primary care physician , su rgeo n, oncologis t, rad iation therapist, or geneticist, result ing in confusio n and unnecessary delay in trea tment.Class ification scheme s are used to provide a foundation for tumor diagn osis with a repro ducible approac h to terminology, whic h aids the clinician in planning treatment, give s an indica tio n of prognosis, allow s for an eva luatio n of the treatment resul ts, and faci litates the easy exc hange of information between the ever-expanding numb er of physicians and health care providers invo lved in treatin g patients effectively. Frequently, patients are referre d for outside opinions or to a tertiary med ical ce nter for treatment. Utilization of similar termin ology by eac h of the faci lities strea mlines the patient 's treatm ent.Th e World Health Organization (WHO) has been at the forefro nt of tum or classification since it began the first Internat ional Histological Class ification of Tumours ser ies back in 1967. The first book devoted to head and neck tumors, publi shed in 1971 , was on the histolo gic typing of oropharyngea l tumors. It includ ed 40 color plates and was published in mult iple langu ages, at a cost of $4. Cont ributing path ologists were fro m II co untries. Thi rtyfou r years later, with a num ber of iterations between , the WHO has j ust (Se ptember 2005) published a new volume on the histologic and genetic typing of tu mors, Pathology and Genetics ofHead and Neck Tumours. Prepared by 130 authors from 28 cou ntries, this aut horitative and co ncise volume provides an international sta nda rd reference book on tumors of the head and neck. The diagnostic criter ia, pathologic fea tures, and associated ge netic alterations were deve loped further by conve ning a Working Group of more than 35 highl y res pecte d authorities fro m mult iple disciplin es in medicine at an Editorial and Consensus Co nference. Th ey ca refully adj usted and clarified the exac t term s to be included .

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Laryngeal spindle cell (sarcomatoid) carcinomas are uncommon tumors, frequently misdiagnosed as reactive lesions or mesenchymal malignancies. The records of 187 patients with tumors diagnosed as laryngeal spindle cell (sarcomatoid) carcinoma were retrieved from the files of the Otorhinolaryngic Tumor Registry of the Armed Forces Institute of Pathology. There were 174 men and 13 women, 35-92 years of age (average, 65.6 years). Nearly all patients experienced hoarseness (n = 165 [88%] patients) for a mean duration of 11.0 months. Patients admitted to smoking (n = 162 [87%] patients) and/or alcohol use (n = 90 [48%] patients). Most tumors were glottic (n = 132 [71%]), T1 (n = 111 [59%]), 1 and polypoid (n = 185 [99%]), with a mean tumor size of 1.8 cm. Histologically, squamous cell carcinoma (n = 157 [84%]) was noted, ulcerated, and blended with the spindle cell component, which was most frequently arranged in a storiform pattern (n = 92 [49%] tumors). Foci of benign or malignant cartilage and/or bone (n = 13 [7%]) were noted in the spindle cell component. All patients were treated with surgery (n = 90 [48%] patients) or surgery with radiation (n = 97 [52%] patients). Recurrences developed in 85 (45%) patients. Overall, T1 glottic tumors managed by complete surgical eradication had the best outcome (mean follow-up, 7.8 years).

Primary angiosarcoma of the spleen is a rare neoplasm that has not been well characterized. We describe the clinical, morphologic, and immunophenotypic findings of 28 cases of primary splenic angiosarcoma, including one case that shares features of lymphangioma/lymphangiosarcoma. The patients included 16 men and 12 women, aged 29 to 85 years, with a mean of 59 years and median of 63 years. The majority of patients (75%) complained of abdominal pain, and 25% presented with splenic rupture. The most common physical finding was splenomegaly (71%). Seventeen of 21 patients were reported to have anemia. Macroscopic examination showed splenomegaly in 85% cases. Sectioning revealed discrete lesions in 88% of cases, ranging from well-circumscribed firm nodules to poorly delineated foci of necrosis and hemorrhage associated with cystic spaces. Microscopically, the tumors were heterogenous; however, all cases demonstrated at least a focal vasoformative component lined by atypical endothelial cells. Solid sarcomatous, papillary, and epithelioid growth patterns were observed. The solid sarcomatous component resembled fibrosarcoma in two cases and malignant fibroushistiocytoma in one case. Hemorrhage, necrosis, hemosiderin, extramedullary hematopoiesis, and intracytoplasmic hyaline globules were frequently identified. A panel of immunohistochemical studies revealed that the majority of tumors were immunoreactive for at least two markers of vascular differentiation (CD34, FVIIIRAg, VEGFR3, and CD31) and at least one marker of histiocytic differentiation (CD68 and/or lysozyme). Metastases developed in 100% of patients during the course of their disease. Twenty-six patients died of disease despite aggressive therapy, whereas only two patients are alive at last follow-up, one with disease at 8 years and the other without disease at 10 years. In conclusion, primary splenic angiosarcoma is an extremely aggressive neoplasm that is almost universally fatal. The majority of splenic angiosarcomas coexpress histiocytic and endothelial markers by immunohistochemical analysis, which suggest that some tumors may originate from splenic lining cells.

Few neoplasms are unique to the sinonasal tract, but sinonasal undifferentiated carcinoma and olfactory neuroblastoma are malignant tumors which require unique management. Due to the rarity of these tumors, practicing pathologists are not always aware of their distinctive clinical, radiographic, histologic, immunohistochemical, and molecular features. These cases are frequently submitted for consultation, further suggesting the diagnostic difficulties inherent to these tumors. Specifically, olfactory neuroblastoma is a neoplasm that can histologically mimic many tumors within the sinonasal tract, making recognition of this tumor important, as the management frequently requires a bicranial-facial surgical approach, a trephination procedure which can be quite technically difficult and challenging to achieve a good result. The management is therefore quite unique in comparison to other sinonasal tract malignancies, setting it apart diagnostically and managerially from other lesions.