Different Keratin Profilesin Craniopharyngioma Subtypes and Ameloblastomas

Craniopharyngiomas are generally considered to arise from the remnants of Rathke's pouch or a misplaced enamel organ. We tried to refine these hypotheses, comparing the subtypes of craniopharyngioma with Rathke's cleft cyst, a known Rathke's pouch derivative, and with ameloblastoma, an enamel organ derivative. Nineteen craniopharyngiomas (14 adamantinomatous and 5 papillary type tumors) and 17 ameloblastomas were immunostained for cytokeratin (CK) 7, CK 8, CK 14, and human hair keratin (HHK). All cases of adamantinomatous craniopharyngioma were CK 7+/CK 8+/CK 14+. Two cases (40%) of papillary craniopharyngioma were CK 7+/CK 8+/CK 14+, whereas the remaining three cases (60%) were CK 7+/CK 8-/CK 14+. Fifteen cases (88%) of ameloblastoma were CK 7-/CK 8+/CK 14+. Only the shadow cells present in adamantinomatous craniopharyngiomas were positive for HHK, which may indicate their follicular differentiation. In Rathke's cleft cyst, ciliated cuboidal cells were CK 7+/CK 8+/CK 14- and metaplastic squamous cells were CK 7+/CK 8/CK 14+. These findings suggest that both subtypes of craniopharyngioma may differ from ameloblastoma in histogenesis, although cytokeratin expression patterns may change during tumor development. Adamantinomatous craniopharyngioma may be related to a heterotopic ectodermal tissue which can differentiate into hair follicles, while papillary craniopharyngioma may arise from Rathke's cleft cyst.     

Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations

Craniopharyngioma is a rare tumor occurring in the sellar region comprising 3% of all intracranial tumors. To elucidate the contribution of beta-catenin gene mutation to tumorigenesis, we examined genetic alterations and expression of beta-catenin in 10 cases of adamantinomatous and 6 cases of papillary craniopharyngiomas. Beta-catenin gene mutations were found in all of the adamantinomatous and none of the papillary craniopharyngiomas. Immunohistochemically, all cases of adamantinomatous craniopharyngioma showed cytoplasmic and nuclear expression of beta-catenin. In contrast, papillary craniopharyngiomas showed exclusively membranous expression. The results suggest that adamantinomatous- and papillary-type craniopharyngiomas are not only clinicopathologically, but also genetically, distinctive variants. Mutation of the beta-catenin gene therefore seems to play an important role in the tumorigenesis of adamantinomatous craniopharyngioma. Among the adamantinomatous-type tumors, beta-catenin-positive mesenchymal cells were observed in two cases. Microdissection-based mutational analysis revealed that these mesenchymal cells also harbor the same beta-catenin gene mutations as those of epithelial cells, suggesting their tumorous nature. Thus, at least a subset of adamantinomatous craniopharyngioma is considered to be biphasic.     

Possible linkage between specific histological structures and aberrant reactivation of the Wnt pathway in adamantinomatous craniopharyngioma

This study concerns the significance of nuclear/cytoplasmic expression of beta-catenin and mutation of the beta-catenin gene in craniopharyngiomas. Fourteen adamantinomatous type and one squamous papillary type craniopharyngiomas were studied. Histologically, 13 of 14 adamantinomatous type craniopharyngiomas showed typical features, ie mixtures of 'palisading cells', 'stellate cells', and 'ghost cells'. In addition, 'whorl-like arrays' of epithelial cells were frequently observed in the areas of stellate cells. On immunohistochemistry, all typical adamantinomatous type craniopharyngiomas showed nuclear/cytoplasmic expression of beta-catenin predominantly in cohesive cells within the whorl-like arrays and in cells transitional towards ghost cells, where immunoreactivity for Ki-67 was almost absent. The cohesive cells in the whorl-like arrays also demonstrated loss of cytokeratin isoform expression. Using direct sequencing of amplified nucleic acids, nine of the 13 typical adamantinomatous type craniopharyngiomas with nuclear beta-catenin accumulation showed heterozygous one-base substitution mutation of the beta-catenin gene. The other unusual adamantinomatous type and squamous papillary type craniopharyngiomas showed no obvious nuclear/cytoplasmic beta-catenin immunoreactivity and no mutation of the beta-catenin gene, suggesting molecular heterogeneity. These findings suggest that the pathogenesis of typical adamantinomatous type craniopharyngioma is associated with abnormalities of Wnt signalling that act as a morphogenetic signal towards whorl-like arrays and ghost cells rather than as simple proliferation stimuli.     

Odontogenic classification of craniopharyngiomas: a clinicopathological study of 54 cases

Based on the striking histological similarity of craniopharyngiomas and some odontogenic tumours, we reclassified a series of 54 craniopharyngiomas (52 adamantinomatous and two papillary variants) according to the WHO classification of odontogenic tumours. Twenty-seven tumours (50%) corresponded histologically to calcifying odontogenic cyst, 13 tumours (24%) to ameloblastoma, and eight (15%) tumours showed features of both calcifying odontogenic cyst and ameloblastoma either within the same specimen or in specimens derived from different resections. Rare tumours included three cases resembling calcifying epithelial odontogenic tumour and one case resembling adenomatoid odontogenic tumour. No odontogenic counterpart could be established for papillary craniopharyngiomas. The two major subtypes, i.e. craniopharyngioma corresponding to calcifying odontogenic cyst and craniopharyngioma corresponding to ameloblastoma, did not differ in their basic clinical features. Our data confirm and extend the close histological resemblance between adamantinomatous craniopharyngioma and odontogenic tumours and cysts. Furthermore, although calcifying odontogenic cyst and ameloblastoma arising in the jaw differ in clinical presentation and outcome, our study did not reveal clinical differences for the corresponding subtypes of craniopharyngioma.     

Collision Tumors of the Sella: Craniopharyngioma and Silent Pituitary Adenoma Subtype 3: Case Report

Collision tumors of the sella turcica are rare and consist mainly of more than one type of pituitary adenoma, usually a corticotropin- and a prolactin-producing adenoma. The association of a craniopharyngioma and a pituitary adenoma is rare. Herein, we report the first case of an association between craniopharyngioma and silent pituitary adenoma subtype 3. It involved a 12-year-old boy who underwent a frontal craniotomy with surgical removal of a calcified sellar tumor. Histology revealed an adamantinomatous craniopharyngioma; however, by electron microscopy, there was conclusive evidence of adenoma cells showing the ultrastructural features of silent pituitary adenoma subtype 3. Endocrine and neuroimaging as well as detailed immunohistochemical and ultrastructural studies were undertaken. The literature is also reviewed.     

Expression of epithelial cell adhesion molecule and pituitary tumor transforming gene in adamantinomatous craniopharyngioma and its correlation with recurrence of the tumor

Craniopharyngiomas are benign tumors of the sellar region generally associated with endocrine disorders and often locally aggressive. The reliable criteria for predicting the tumor behavior are still lacking. It has been suggested that proliferative potential of the tumor cells is necessary for recurrence. The aim of this study was to evaluate the activity and correlation of epithelial cell adhesion molecule (Ep-CAM) and pituitary tumor transforming gene (PTTG-1) immunoexpression that is possibly related to relapse in 40 patients with adamantinomatous craniopharyngioma. The study involved clinical and pathologic analysis. Of the subjects, 49% were females and 51% were males. The mean age of the patients was 37 years. Relapsing rate at 5 years was 46% and for death was 22.5%. Histologically, whorl-like arrays and dense or hypercellular stellate reticulum cells were correlated with recurrence. Epithelial CAM and PTTG-1 were also higher in stellate reticulum cells and in whorl-like arrays. Both were higher in recurrence/regrowth tumors than in primary one. The PTGG-1 expression in craniopharyngioma may suggest hypophyseal metaplasia. The Ep-CAM and PTTG-1 expression in craniopharyngioma could be used as prediction markers of relapsing tumor. It has been suggested that proliferative potential of the tumor cells is necessary for recurrence.     

Epithelial–mesenchymal transition and clinicopathological correlation in craniopharyngioma

Qi S‐T, Zhou J, Pan J, Zhang C, Silky C & Yan X‐R (2012) Histopathology 61 , 711–725
Epithelial–mesenchymal transition and clinicopathological correlation in craniopharyngioma Aims: To assess the immunophenotypic changes associated with epithelial–mesenchymal transition (EMT) in craniopharyngioma, especially at the tumour invasive front, and to correlate the findings with clinicopathological features and patient outcomes. Methods and results: Forty‐two craniopharyngiomas were investigated for the presence of EMT markers (vimentin, E‐cadherin and β‐catenin) by immunohistochemistry and western blot. The relationships between expression of these markers and various clinicopathological indicators and clinical outcomes of the tumours were analysed. There were statistically significant differences in the expression of vimentin and E‐cadherin–β‐catenin between adamantinomatous and papillary variants. The expression of vimentin and E‐cadherin (but not that of β‐catenin) in whole tumour sections was associated with tumour recurrence, and with postoperative weight and hypothalamic disturbances; the expression of vimentin and E‐cadherin–β‐catenin at the tumour invasive front was also associated with tumour recurrence, postoperative weight, and hypothalamic disturbances. The results from western blotting closely matched those of immunohistochemistry. Conclusions: Our study demonstrates, for the first time, the potential prognostic implications of vimentin, E‐cadherin and β‐catenin expression in craniopharyngiomas. EMT may represent a crucial mechanism in the progression of craniopharyngiomas.     

Malignant craniopharyngioma

Craniopharyngiomas are histologically and cytologically benign epithelial tumors of the central nervous system that may be locally aggressive and tend to recur after excision. Malignant change in craniopharyngiomas is extremely rare; we found only 4 such reports in the literature. In this report, we describe a case of squamous cell carcinoma arising in a previously benign craniopharyngioma in a 42-year-old woman. The patient was diagnosed with craniopharyngioma in 1982; during the subsequent 15 years she experienced 7 tumor recurrences, for which surgical resections and 3 courses of radiotherapy were performed. In 1998, the tumor recurred with involvement of the nasal cavity and sphenoid and ethmoid sinuses. Histologic evaluation revealed foci of typical adamantinomatous craniopharyngioma associated with a moderately differentiated squamous cell carcinoma. The transition of typical craniopharyngioma to squamous cell carcinoma was well demonstrated, suggesting that carcinoma arose from the underlying craniopharyngioma. Radiation may have been a contributing factor to carcinogenesis in this case.     

眉弓入路显微手术治疗颅咽管瘤的临床应用及疗效

目的　分析眉弓入路显微手术治疗颅咽管瘤的临床效果及优势。 方法　选择2016年3月~2018年3月于本院接受眉弓锁孔入路显微手术治疗的颅咽管瘤患者20例为观察组，2015年1月~2016年2月于本院接受经冠状额下入路手术治疗的颅咽管瘤患者15例为对照组。比较两组的手术指标、肿瘤切除完整、症状改善以及并发症等情况。 结果　观察组手术时间、手术切口长度、住院时间均短于对照组，术野暴露程度满意度95.00%，高于对照组的66.67%（P<0.05），输血例数、治疗费用少于对照组。两组患者的颅咽管瘤全切除率比较，无统计学差异（P＞0.05）。出院随访3个月，观察组的头痛、内分泌症状改善效果优于对照组（P<0.05），而嗅觉障碍、视力减退、多尿症状比较，无统计学差异（P>0.05）。观察组患者的并发症发生率为20.00%，低于对照组的66.67%（P<0.05）。 结论　经眉弓入路锁孔显微技术治疗颅咽管瘤，可获得良好的手术视野，脑组织损伤小，手术时间、住院时间较短，治疗费用、输血例数较少，头痛、内分泌症状明显改善，并发症发生率较低，值得推广。     

Outcome of postoperative intratumoral bleomycin injection for cystic craniopharyngioma

Total excision is a treatment of choice in preventing the relapse of craniopharyngioma, but for tumors involving an extensive area, it is often associated with an increased risk of complications. We have performed a partial or subtotal tumor removal followed by repeated injection of bleomycin into the remaining tumor through a subcutaneous reservoir as postoperative adjuvant therapy. A retrospective review of clinical, radiological, and surgical data was performed for 10 patients (5 males and 5 females; age, 3-65 yr; follow-up duration, 12-79 months) with cystic craniopharyngiomas. The measurements of lactate dehydrogenase (LDH) level at each aspiration were performed. The shrinkage and/or stabilization of tumor was initially noted in all cases. The recurrence of tumor was seen in 4 cases (40%). The decreased or increased level of LDH was interpreted as tumor shrinkage or recurrence, respectively. The transient toxic reactions were observed in 3 patients (30%). Our study demonstrates that postoperative bleo-mycin injection for cystic craniopharyngioma, although does not appear to eradicate the tumor, decreases and stabilizes the tumor size, when used as an adjuvant therapy in young patients.     

Expression of leukemia inhibitory factor in craniopharyngioma

It has recently been reported that overexpression of leukemia inhibitory factor (LIF) in mice transgenic for LIF causes invagination of the anterior wall of Rathke’s pouch leading to the formation of cysts lined by LIF immunoreactive epithelial cells. Strong immunoreactivity was also found in human Rathke’s cleft cysts. Because such cysts and craniopharyngiomas share a common histogenesis, we raised the question of whether LIF is also expressed in craniopharyngioma. Fourteen histologically verified craniopharyngiomas of adamantinomatous type were examined for LIF immunoreactivity using the streptavidin-biotin-peroxidase complex method. Rabbit-anti-LIF antibody dilution 1:40) was applied to tissues having undergone antigen retrieval (microwaving in citrate buffer at pH 6). For positive control, nontumorous pituitary tissues were used. Primary antibody substituted with phosphate-buffered saline served as a negative control. By immunocytochemistry, the epithelial cells of all 14 craniopharyngiomas were LIF immunoreactive, showing varying degrees of staining intensity. In comparison, the connective tissue components of the tumors were immunonegative. Our study provides evidence that LIF is expressed in the epithelial cells of craniopharyngioma. Further investigation is required to elucidate the possible role of LIF in the development and progression of craniopharyngiomas.     

Mutational activation of BRAF is not a major event in sporadic childhood papillary thyroid carcinoma.

Papillary thyroid carcinoma may encompass a mixed group of neoplasms where divergence in clinical behavior may reflect distinct genetic alterations. For example, young patients with papillary thyroid carcinoma have a better prognosis than affected adults, and their carcinomas are much more likely to harbor chromosomal rearrangements involving the RET proto-oncogene. Mutational activation of the BRAF oncogene has recently been identified as the most common genetic alteration in papillary thyroid carcinoma, but little is known about its frequency as a function of patient age. We tested 20 papillary thyroid carcinomas from young patients ranging from 10 to 17 years of age for the thymine (T) --> adenine (A) missense mutation at nucleotide 1796 in the BRAF gene using a newly developed assay that employs a novel primer extension method (Mutector assay). The prevalence of BRAF mutation was compared with a larger group of papillary thyroid carcinomas from previously tested adult patients (>20 years). BRAF mutations were not common in papillary thyroid carcinomas from young patients compared to their counterparts in adults (20 vs 77%; OR=13.3, 95% confidence interval (CI)=3.4-56.5; P<0.0001), but they become increasingly prevalent with advancing patient age (OR as a function of age at 10-year intervals=1.80 CI=1.33-2.44; P<0.001). Unlike papillary thyroid carcinomas that arise in adults, mutational activation of BRAF is not a major genetic alteration in papillary thyroid carcinomas that arise in young patients. The increasing frequency of BRAF mutations as a function of age could help account for the well documented but poorly understood observation that age is a relevant prognostic indicator for patients with papillary thyroid carcinoma.     

Spontaneous Alteration from Rathke’s Cleft Cyst to Craniopharyngioma—Possible Involvement of Transformation Between These Pathologies

Both Rathke’s cleft cyst and craniopharyngioma are considered to arise from the remnants of Rathke’s diverticulum despite the quite different histological characteristics. These two lesions may consist of a disease spectrum extending from Rathke’s cleft cyst to craniopharyngioma. However, in spite of increasing evidence of these intermediate histologies, very few cases of the actual transformation from Rathke’s cleft cyst to craniopharyngioma have been reported in the same patient. A 47-year-old man suffered from recurrent visual dysfunction. Aspiration and partial cystectomy was performed to a suprasellar massive cystic lesion. The histological diagnosis was Rathke’s cleft cyst with a small component of squamous metaplasia. Seven months later, the cyst was re-expanded. The cyst wall was irregularly thickened. Re-operation was performed, and the thickened anterior wall was widely removed. Postoperative histological examination showed multiplication of stratified squamous epithelia forming a papillary arrangement. Ki-67 staining showed positive cells randomly distributed not only in the basal layer but also in various epithelial layers, with a labeling index of more than 20 %. The histological diagnosis was squamous papillary type of craniopharyngioma with high potential of proliferation. Subsequent immunohistochemical examinations showed positive reaction to cytokeratin 8 only in the initial epithelium and negative in the latter epithelium. The present case was thought as an actual evidence of the proposed link between Rathke’s cleft cyst and craniopharyngioma. Cytokeratin 8 could be the important examination to differentiate Rathke’s cleft cyst from craniopharyngioma.     

MRI影像分型对布鲁杆菌病性脊椎炎的诊断与治疗价值

目的 探讨MRI影像分型对布鲁杆菌病性脊椎炎(BS)的诊断与治疗价值。方法 回顾性分析2002年1月—2013年7月确诊且符合纳入标准的257例BS患者的临床资料,其中男131例,女126例,年龄21～82岁,平均(46.52±1.27)岁。依据发病部位、椎体及椎间隙炎症浸润和破坏程度、椎旁软组织改变、脊柱的稳定性、脊髓或马尾、神经根受压等MRI影像表现对病例进行分型。采用非手术和手术治疗,前者为单纯药物治疗(A组),后者分为腰椎局限性病灶微创术(B组)、颈椎病灶清除植骨内固定术(C组)、胸腰椎病灶清除植骨术(D组)和胸腰椎病灶清除植骨内固定术(E组)。通过影像分析一致性检验及临床疗效判定标准对影像分型与临床治疗策略两者之间的相关性进行评价。结果 本组257例中,MRI影像分型为Ⅰ型47例、Ⅱ型45例、Ⅲ型41例、Ⅳ型32例、Ⅴ型92例;2个椎体受累241例、3个椎体受累16例,以腰椎发病率最高(65.36%,168/257)。治疗后3个月257例均得到复查;6个月212例(82.49%)得到复查,其中手术134例、非手术78例,A组5例复发(腰椎Ⅱ型1例、Ⅲ型2例、Ⅳ型2例)、B组2例复发(腰椎Ⅱ型1例、Ⅳ型1例),复发7例均改为E组治疗方案治愈;12个月173例(67.31%)得到复查,其中手术112例、非手术61例,各组均无复发病例。C、E组无论术后早期还是后期脊柱均稳定,且植骨均愈合;D组56例中50例采用横突关节突间植骨术,19例(38%)植骨愈合且脊柱稳定,31例(62%)植骨吸收(其中16例伴有脊柱不稳及下腰痛,再次行E组治疗方案后植骨融合脊柱稳定)。影像分析一致性检验κ值均>0.75;临床疗效显示各组后一个时间点与前一个时间点治愈率比较差异均有统计学意义(P值均＜0.05);在复检时间点C、E组治愈率高于A、B、D组,D、E 2组6个月、12个月治愈率比较差异均有统计学意义(P值均＜0.05)。结论 BS MRI影像学分型具有特征性,有助于临床诊断及鉴别诊断,各型均有适合的治疗方法,以Ⅰ型非手术治疗,Ⅱ、Ⅳ型微创术,Ⅲ、Ⅴ型病灶清除植骨内固定术为佳。     

Pseudomyxoma peritonei (mucinous carcinoma peritonei) preceded by intraductal papillary neoplasm of the bile duct

Pseudomyxoma peritonei (mucinous carcinoma peritonei) is a rare clinical disease. Although most cases derive from appendiceal mucinous tumors, a few are associated with pancreatic intraductal papillary mucinous neoplasms. Intraductal papillary neoplasms of the bile duct share many similarities with pancreatic intraductal papillary mucinous neoplasms and are thought to be their biliary counterparts. We report a case of low-grade intraductal papillary neoplasm of the bile duct who developed pseudomyxoma peritonei 6 years after surgical treatment of the primary biliary tumor. To the best of our knowledge, this is the first case of pseudomyxoma peritonei associated with intraductal papillary neoplasm of the bile duct. The tumor recurrence in our case may be due to tumor spillage at the time of the first surgery, since there is no recurrent biliary tumor in the preserved liver lobe. Prevention of spillage of epithelial cell-containing mucin during surgical operations is important in treating intraductal papillary neoplasms of the bile duct.     

Beta-catenin mutations are frequent in calcifying odontogenic cysts, but rare in ameloblastomas

We have reported previously that alterations to beta-catenin occur frequently in adamantinomatous craniopharyngioma. Based on its histological resemblance to some odontogenic tumors, we suspected the presence of common genetic alterations among these tumors. To address this issue, 11 cases of calcifying odontogenic cyst (COC) and 20 cases of ameloblastoma were investigated for the presence of beta-catenin mutations and beta-catenin expression. Ten COCs were successfully analyzed by direct sequencing, and nine of them were found to harbor somatic beta-catenin mutations. Immunohistochemically, all of the COCs showed nuclear and cytoplasmic expression of beta-catenin with a heterogeneous pattern. No beta-catenin mutations were found in ameloblastomas, except for one case of the follicular type. All follicular ameloblastomas exhibited moderate nuclear and cytoplasmic accumulation of beta-catenin, in contrast to the predominantly membranous expression seen in the plexiform type. beta-Catenin mutation is considered to be a characteristic genetic feature of COC, and may play a critical role in its histogenesis. Although ameloblastoma closely resembles COC histologically, the two have genetically distinctive features.     

High-grade papillary urothelial carcinoma of the urinary tract: a clinicopathologic analysis of a post-World Health Organization/International Society of Urological Pathology classification cohort from a single academic center

About one half of all bladder neoplasms are noninvasive, and in those, the histologic grade is a crucial prognosticator. Few single-center studies have assessed the recurrence, progression, and cancer-related mortality rates of noninvasive high-grade papillary urothelial carcinomas. With this aim, we evaluated the clinicopathologic and outcome features of 85 patients with high-grade papillary urothelial carcinoma. Median age was 68 years, and 80.5% were men. Tumor size ranged from 0.3 to 13.0 cm (median, 1.6 cm). Recurrence was found in 36.5% of the patients, whereas tumor progression, defined as invasion of lamina propria or beyond, was identified in 40% of all cases. When present, lesion reappearance involved mostly 1 to 2 episodes. Metastasis appeared in 20% of the patients, and 15% died of disseminated bladder cancer. All cancer-related deaths occurred in the group of patients with progression, whereas patients with recurrence showed similar outcomes to those with no recurrence. For patients with tumor progression, clinical stage was significantly associated with outcome (P = .002). As for prognosis, tumor size was strongly associated with progression (P < .01). In conclusion, recurrence, progression, and cancer-specific mortality rates were 36.5%, 40%, and 15%, respectively. All the patients who died of cancer had a history of tumor progression. Patients with recurrences showed similar outcomes to those with no recurrence. Tumor size was strongly associated with tumor progression and cancer-specific survival, whereas clinical stage was significantly associated with outcome in the progression group. In light of the high recurrence and progression rates of high-grade papillary urothelial carcinoma, strict clinical surveillance aimed to detect early recurrent lesions, especially in patients with larger tumors, is warranted.     

Thyroid nodules with FNA cytology suspicious for follicular variant of papillary thyroid carcinoma: follow-up and management

Thyroid nodules diagnosed as follicular neoplasm on fine-needle aspiration biopsy (FNAB) may represent hyperplastic/adenomatous nodules, follicular adenoma or carcinoma, and follicular variants of papillary thyroid carcinoma (FVPTC) on histologic follow-up. In our laboratory, we attempted to identify a subset of cases which showed cellular specimens with focal features (nuclear chromatin clearing, membrane thickening, and rare grooves) suspicious for the follicular variant of papillary thyroid carcinoma. These cases are reported as follicular-derived neoplasms with nuclear features suspicious for FVPTC to distinguish them from those diagnosed as follicular neoplasm. This study documents our experience with 52 cases so diagnosed and followed prospectively with histologic follow-up. A neoplastic nodule was confirmed in 45/52 cases (86%), of which 40 were malignant (77%). FVPTC was identified in 35/52 cases (67%). Four cases were usual papillary carcinoma, 3 were follicular adenoma, 2 were Hürthle-cell adenoma, and 1 was insular carcinoma. In 7 cases, the subsequent histologic findings were nonneoplastic (5 hyperplastic nodules and 2 colloid nodules). Our prospective study shows that in cellular smears from thyroid nodules, a careful search for the nuclear features of papillary carcinoma should be performed, and it is appropriate to diagnose cases as suspicious for FVPTC if the nuclear features of papillary carcinoma are focal. The surgical management of this group may include an intraoperative confirmation of cytologic diagnosis by scrape preparation and/or frozen section in order to avoid a second surgical intervention for completion thyroidectomy.