Elastin in pulmonary pathology: relevance in tumours with a lepidic or papillary appearance. A comprehensive understanding from a morphological viewpoint.

Elastin and collagen are the main components of the lung connective tissue network, and together provide the lung with elasticity and tensile strength. In pulmonary pathology, elastin staining is used to variable extents in different countries. These uses include evaluation of the pleura in staging, and the distinction of invasion from collapse of alveoli after surgery (iatrogenic collapse). In the latter, elastin staining is used to highlight distorted but pre-existing alveolar architecture from true invasion. In addition to variable levels of use and experience, the interpretation of elastin staining in some adenocarcinomas leads to interpretative differences between collapsed lepidic patterns and true papillary patterns. This review aims to summarise the existing data on the use of elastin staining in pulmonary pathology, on the basis of literature data and morphological characteristics. The effect of iatrogenic collapse and the interpretation of elastin staining in pulmonary adenocarcinomas is discussed in detail, especially for the distinction between lepidic patterns and papillary carcinoma.

Intraductal Adenocarcinoma of the Prostate With Cribriform or Papillary Ductal Morphology: Rare Biopsy Cases Lacking Associated Invasive High-grade Carcinoma.

Prostatic duct adenocarcinoma, characterized by pseudostratified columnar epithelium, has historically been considered invasive carcinoma, although it may commonly have an intraductal component. Usual (acinar) intraductal carcinoma of the prostate (IDC-P) is a noninvasive high-risk lesion typically associated with high-grade, high-stage prostate cancer. Whereas there have been rare biopsy studies of pure acinar IDC-P or IDC-P associated with only low-grade carcinoma, there have been no analogous series of IDC-P with cribriform or papillary ductal morphology on biopsy unassociated with invasive high-grade carcinoma. We identified 14 patients with biopsies showing IDC-P with ductal morphology, defined as prostatic duct adenocarcinoma confined to glands/ducts with immunohistochemically proven retention of basal cells. Our series includes 12 patients with pure IDC-P and 2 patients with concurrent low-volume Grade Group 1 invasive cancer in unassociated cores. Three patients underwent radical prostatectomy: 2/3 had high-grade cancer in their resection specimen (Grade Group 3, Grade Group 5), including 1 with advanced stage and nodal metastases; 1/3 had Grade Group 1 organ-confined carcinoma and spatially distinct IDC-P with ductal morphology. Five men had only follow-up biopsies: 2/5 had cancer (Grade Group 2, Grade Group 4); 1/5 had IDC-P (on 2 repeat biopsies); and 2/5 had benign transurethral resection of the prostate. In all 5 cases with invasive cancer, the invasive portion was comprised purely of acinar morphology; no invasive ductal component was identified. Five patients did not have follow-up biopsies and were treated with radiation therapy±androgen deprivation. One patient had no follow-up information. In an analogous situation to acinar IDC-P, we propose that rarely there is a precursor form of ductal adenocarcinoma that can exist without concurrent invasive high-grade carcinoma and propose the term "IDC-P with ductal morphology," consistent with the terminology for acinar prostate adenocarcinoma. Until more evidence is accumulated, we recommend reporting and treating patients with IDC-P with ductal morphology in a manner analogous to those with acinar IDC-P. As with pure IDC-P with acinar morphology, we would also recommend not grading pure IDC-P with ductal morphology. Finally, we propose a new addition to the diagnostic criteria of IDC-P to include intraductal lesions with ductal morphology consisting of papillary fronds or cribriform lesions lined by cytologically atypical pseudostratified epithelium.

Minor components of micropapillary and solid subtypes in lung invasive adenocarcinoma (≤ 3 cm): PET/CT findings and correlations with lymph node metastasis.

OBJECTIVE: To investigate the PET/CT findings in lung invasive adenocarcinoma with minor components of micropapillary or solid contents and its association with lymph node metastasis. MATERIALS AND METHODS: A total of 506 lung invasive adenocarcinoma (≤ 3 cm) patients who underwent a PET/CT examination and resection surgery were included. According to the proportion of solid/micropapillary components, the patients were classified into three groups: solid/micropapillary-negative (SMPN) (n = 258), solid/micropapillary-minor (SMPM; > 5% not predominant) (n = 158) and solid/micropapillary-predominant (SMPP; > 5% most dominant) (n = 90). The patients' PET/CT findings, including SUVmax, MTV, TLG and CT characteristics, and other clinical factors were compared by one-way ANOVA test. Logistic regression analysis was done to identify the most predictive findings for lymph node metastasis. RESULTS: The value of SUVmax, MTV, TLG and tumor size was highest in SMPP group, followed by SMPM and SMPN group (P < 0.001).The areas under the curve for SUVmax, MTV and TLG for node metastasis were 0.822, 0.843 and 0.835, respectively. Univariate analysis found that the SMPP and SMPM group had more lymph node metastasis than the SMPN group (P < 0.001). Furthermore, the lymph node metastasis group had higher CEA, SUVmax, MTV, TLG, tumor size and more pleural invasion (P < 0.001). Logistic regression analysis found that SMPP pathological type, SMPM pathological type, higher CEA and male patients were risk factors for lymph node metastasis (P < 0.01). CONCLUSIONS: Lung invasive adenocarcinoma with micropapillary or solid contents had higher SUVmax, MTV, TLG and tumor size and was associated with lymph node metastasis, even if they were not predominant.

Pancreatobiliary-type intraductal papillary mucinous neoplasm of the pancreas may have 2 subtypes with distinct clinicopathologic and genetic features.

We recently experienced cases of pancreatobiliary-type intraductal papillary mucinous neoplasms (PB-IPMNs) with imaging features resembling pancreatic ductal adenocarcinomas (PDACs), and histologic appearance of purely pancreatobiliary morphology and highly distorted papillary growth, which led to the present study aiming to systematically investigate PB-IPMNs in comparison with PDACs. Surgical cases of PB-IPMNs (n = 31) and PDACs (n = 24) were examined. PB-IPMNs were classified into monotypic tumors (n = 12; 39%) consisting of entirely high-grade pancreatobiliary-type neoplastic cells and polytypic cases (n = 19; 61%) associated with components of low-grade dysplasia and/or other histologic types (eg, gastric, intestinal, or oncocytic types). Clinically, monotypic PB-IPMNs less commonly had dilatation of the ampullary orifice (0% versus 74%) and mucin hypersecretion (17% versus 89%) than did polytypic cases. In most cases of monotypic PB-IPMNs, cystic dilatation of the lesional ducts was less obvious on imaging; therefore, 33% were radiologically diagnosed as PDACs. Histologically, intraductal tumors in monotypic cases showed a highly complex papillary architecture with tubular/cribriform glands and irregular branching, and all these cases were associated with invasive malignancy. GNAS mutations were detected in polytypic PB-IPMNs (6/19; 32%), but there were no GNAS mutations in monotypic cases. The recurrence-free survival of patients with monotypic PB-IPMN or PDAC was similar and significantly worse than that of patients with polytypic PB-IPMN. In conclusion, some cases of monotypic PB-IPMNs lacked the classic characteristics of IPMNs and shared features with PDACs, raising the possibility that these cases may be better classified as a papillary variant of PDACs rather than IPMNs.

Second predominant subtype predicts outcomes of intermediate-malignant invasive lung adenocarcinoma†.

OBJECTIVES: Acinar predominant and papillary predominant invasive adenocarcinomas are likely to be classified as intermediate-malignant types. Although these two types of adenocarcinoma are distinguished morphologically, the differences between their malignant behaviours and prognoses are not clear. The aim of this study is to provide a prognostically relevant stratification of these similar subtypes based on pathological features. METHODS: We retrospectively reviewed 347 consecutive clinically N0M0 lung adenocarcinomas of ≤3 cm in diameter that were resected between April 2006 and December 2010 at two institutes. Acinar and papillary predominant adenocarcinomas were classified into acinar/papillary-lepidic type and acinar/papillary-non-lepidic type according to whether the second predominant component was a lepidic or invasive component. RESULTS: Fifty-four acinar and 59 papillary predominant adenocarcinoma cases were classified as acinar/papillary-lepidic type (n = 65) or acinar/papillary-non-lepidic type (n = 48) cases. Acinar/papillary-non-lepidic type cases were accompanied by more vascular invasion (13.8% vs 31.3%, P = 0.0451) and pleural invasion (9.2% vs 25.0%, P = 0.0450) than were acinar/papillary-lepidic type cases. Five-year overall survival (OS) and recurrence-free survival (RFS) also differed significantly between these types (5-year OS: acinar/papillary-lepidic type, 96.3% vs acinar/papillary-non-lepidic type, 61.8%, hazard ratio = 6.315, P = 0.00650; 5-year RFS: acinar/papillary-lepidic type, 91.4% vs acinar/papillary-non-lepidic type, 68.8%, hazard ratio = 2.967, P = 0.0210). Multivariate analysis revealed that a second predominant component was an independent prognostic factor for RFS (acinar/papillary-non-lepidic type: hazard ratio = 3.784, 95% confidence interval 1.091­13.128, P = 0.036). CONCLUSIONS: The pathological second predominant component allows intermediate-malignant adenocarcinomas to be subclassified with prognostic significance. It can be utilized when assessing postoperative risks for recurrence and when considering therapeutic strategies.

Characterization of intraductal papillary neoplasm of bile duct with respect to histopathologic similarities to pancreatic intraductal papillary mucinous neoplasm.

Intraductal papillary neoplasm of bile duct (IPNB) is a papillary tumor covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bile ducts. It reportedly shows similarities to intraductal papillary mucinous neoplasm of pancreas (IPMN), to various degrees. Herein, IPNB was pathologically analyzed by classifying 52 cases into 4 groups based on the histopathologic similarities to IPMN: group A (identical to IPMN, 19 cases), group B (similar to but slightly different from IPMN, 18 cases), group C (vaguely similar to IPMN, 5 cases), and group D (different from IPMN, 10 cases). In group A, intrahepatic and perihilar regions were mainly affected, most cases were of low/intermediate or high grade without invasion, and gastric type was the most common phenotype, followed by oncocytic and intestinal types. In groups C and D, perihilar and distal bile ducts were affected, almost all cases were of high grade with invasion, and most of them were of intestinal and pancreatobiliary phenotypes. Most group B cases were of intestinal phenotype, and all were of high grade with or without invasion. In conclusion, these 4 groups of IPNB showed unique pathologic features and behaviors. Group A cases were less aggressive and shared many features with IPMN, whereas group C and D cases were more aggressive and mainly found in perihilar and distal bile ducts. Group B resembling IPMN was intermediate between them. This classification may be useful in clinical practice and holds promise for a novel approach to analyze IPNB tumorigenesis.

Distinct patterns of peritumoral histological findings in subtypes of intraductal papillary mucinous neoplasms of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are primary pancreatic neoplasms that can act as precursors to invasive adenocarcinoma of the pancreas. The peritumoral stroma has been increasingly recognized to play an important role in many types of tumors. Therefore, to investigate the clinicopathological significance of the peritumoral stroma in IPMNs, we examined the histological features of the peritumoral stroma in each subtype and histological grade of IPMNs. Eighty-two patients with IPMN, who underwent surgical resection, were reviewed clinicopathologically. Intraductal papillary mucinous neoplasms (86 lesions in total) were histologically subclassified into gastric (n = 51), intestinal (n = 22), pancreatobiliary (n = 11), and oncocytic (n = 2) subtypes. Peritumoral histological features between the gastric and intestinal subtypes were evaluated by each histological grade. The results showed that subepithelial edema and inflammatory cell infiltration were more commonly observed in the gastric subtype (74% and 79%, respectively) than in the intestinal subtype (12% and 25%, respectively) of low-grade IPMNs. On the other hand, mucus lakes were more commonly observed in the intestinal subtype (100%) than in the gastric subtype (0%) of high-grade IPMNs. In addition, pancreatobiliary subtype IPMNs tended to exhibit acute inflammation such as neutrophil predominance. This study showed that peritumoral histological features differed among subtypes of IPMNs from low-grade tumors. These differences suggest the possibility that each subtype of IPMNs has a distinct mechanism from an early stage of tumor progression, which is reflected in the properties of the peritumoral stroma.

Biliary tract intraductal papillary mucinous neoplasm: a brief report and review of literature.

Biliary Tract Intraductal Papillary Mucinous Neoplasm (BT-IPMN) is a very rare entity, gradually emerging into attention as sporadic cases are being reported worldwide. In this brief report we discuss about such an entity from our part of the world, based on a case from our institution. A 47-year-old female was referred to our department with jaundice, intermittent fever with chills and rigor of 6 weeks duration. Initial evaluation revealed obstructive jaundice with distended gall bladder. Imaging with ultrasonogram (USG) and magnetic resonance imaging (MRI) showed hugely dilated intra and extrahepatic biliary radicles with multiple and diffuse soft tissue lesions filling the common bile duct (CBD) extending to the ductal system of left lobe of liver. A side viewing endoscopy demonstrated mucin extruding from a prominent ampulla of Vater. The patient was managed successfully by left hepatectomy with pancreaticoduodenectomy (HPD). Gross pathological examination of the specimen showed marked dilatation of intra and extra hepatic bile ducts with multiple polypoidal lesions and plenty of mucin filling the entire biliary ductal system. Histopathology revealed predominantly intraductal papillary mucinous adenocarcinoma at the hilum extending to left bile duct with diffuse dysplastic changes throughout the biliary tree. Thus the clinical, radiological and pathological features of this lesion clearly fit into the diagnosis of BT-IPMN, which is slowly being established as a definite clinical entity with features much similar to its pancreatic counterpart.

A suggested modification to FIGO stage I endometrial cancer.

OBJECTIVE: FIGO stage I endometrial cancers are divided into two substages, regardless of the presence or absence of lymphovascular space invasion (LVSI). The aim of this study was to investigate whether stratification based on the LVSI status would better predict mortality. METHODS: Using a multicentric database, we identified patients who underwent endometrial cancer operations between 2000 and 2010. The staging performance was quantified with respect to discrimination. RESULTS: The study cohort included 508 patients (198 with LVSI-positive tumors and 310 with LVSI-negative tumors). The survival difference between the stage I patients with LVSI-positive and LVSI-negative tumors was highly significant (81% and 97%, respectively P=.009), whereas the difference between the stage I patients with tumors invading greater or less than half of the myometrium was not (87% and 96%, respectively P=0.09). The 5-year OS rates for the patients with LVSI-negative tumors invading less than half of the myometrium, with LVSI-negative tumors invading more than half of the myometrium and with LVSI-positive invading more than or less than half of the myometrium were 98%, 95%, and 81%, respectively (P=.03). Separating the LVSI-negative and LVSI-positive tumors would improve discrimination (concordance index, 77% vs. 75%, respectively, using the actual staging system). CONCLUSION: A LVSI-positive status has a significantly worse prognosis. In this study, the distinction by LVSI status appears to be more relevant than the distinction between stages IA and IB for predicting survival in stage I endometrial cancer. This difference in prognosis would favor restaging these two entities.

Invasive micropapillary breast carcinoma: a retrospective study of classification by pathological parameters.

Micropapillary breast carcinoma has been recognized as a morphologically and biologically distinct form of breast carcinoma. Although data suggest that patient outcomes in cases of micropapillary breast carcinoma do not differ significantly from other breast carcinomas, the impact that a micropapillary component might have on the pathological work-up of a case of breast carcinoma remains an important point of discussion (especially as pertaining to the risk of lymphovascular disease). In this study, we perform an extensive retrospective study of the pathological parameters of seven years of breast surgical pathology cases to explore the relationship that micropapillary morphology might have with other important pathological parameters of a breast cancer case work-up (e.g. tumour size, lymphovascular invasion, lymph node status). We also analyze our data set to see if a micropapillary component would influence hierarchical classification by pathological parameters. Micropapillary features correlated with a higher frequency of ER positivity and lymphovascular invasion; there was no statistical difference between those cases with and without a micropapillary component from the perspective of other clinicopathological parameters, however. The presence of micropapillary features did influence classification, however, and produced a distinct cluster amidst comparison of other pathological variables.

[Bethesda classification of fine needle punctures of the thyroid. Much ado about nothing really new?]. / Bethesda-Klassifikation der Feinnadelpunktion der Schilddrüse. Viel Lärm um wenig Neues?

The Bethesda system for reporting thyroid cytopathology was published in 2008 (Baloch et al. 2008, Cytojournal 5:6; Baloch et al. 2008, Diagn Cytopathol 36:425-437) offering a classification system which is closely related to clinical data. The aim was to ensure adequate terminology without risk of errors in understanding, to advise clinicians concerning therapeutic options in relationship to cytological diagnoses as well as to facilitate the comparison of cytology data at national and international levels. However, mainly due to specific US American (both medical and legal) demands, this classification system is not yet fully appreciated in most European countries. The reasons are various: (a) Criteria for representative material are much more restrictive than those commonly used and in Germany a higher number of (unnecessary) repunctures would be the consequence. (b) It remains doubtful whether the introduction of a new and rather heterogeneous category of "atypia of undetermined significance or follicular lesion of undetermined significance" would contribute to a substantial decrease of findings classified as "follicular neoplasia". Furthermore it is unlikely that clinicians would be willing to accept the recommended conservative approach with repuncture if a new diagnostic category is associated with a calculated risk of malignancy in 5-15% cases. (c) Until now an integration of new developments in molecular markers into the Bethesda system is missing. Thus, for experienced cytologists the Bethesda system for reporting thyroid cytopathology offers very limited benefits in comparison to the currently used, established and highly accepted classification systems. However, a positive argument remains the fact that an internationally accepted classification system may improve the comparability of the results of national and international studies on thyroid findings.

Claudin-18 in biliary neoplasms. Its significance in the classification of intrahepatic cholangiocarcinoma.

Claudin-18 (CLDN18), a tight junction protein specific to stomach and lung, is aberrantly expressed in preinvasive and invasive neoplasms of the pancreas. To investigate the significance of CLDN18 expression in biliary neoplasms, immunohistochemical analysis was performed. CLDN18 expression was frequently observed in the epithelial cells of extrahepatic bile duct carcinomas (90%, n = 99), intrahepatic intraductal papillary neoplasms of the bile duct (IPNBs, 100%, n = 11), and extrahepatic IPNBs (89%, n = 9), while it was less frequent in intrahepatic cholangiocarcinomas (ICCs, 43%, n = 83). Interestingly, CLDN18 expression was also frequently observed in precancerous lesions such as biliary intraepithelial neoplasias (78%, n = 18). Among ICCs, CLDN18-positive cases showed higher frequencies of periductal infiltrative growth, perineural invasion, and lymph node metastasis. Multivariable analysis demonstrated that positive CLDN18 expression was an independent risk factor for lymph node metastasis in ICCs. Furthermore, CLDN18 expression was associated with poor overall survival by univariable analysis, as well as lymph node metastasis. These results suggest that CLDN18 may play an important role in biliary carcinogenesis, and especially in ICCs, it is associated with aggressive behavior and serves as a useful marker for the classification of ICC.

Gastric micropapillary carcinoma: A distinct subtype with a significantly worse prognosis in TNM stages I and II.

Micropapillary carcinoma (MPC) is an aggressive variant of adenocarcinoma, with a high incidence of lymph node (LN) metastasis in several organs, although not yet well described in the stomach. Thus, we compared the clinicopathologic characteristics, including survival data and immunohistochemical profiles of cell adhesion molecules (E-cadherin, ß-catenin, IQGAP-1, and CD44v6), of MPCs with those of adenocarcinomas lacking MPC components (non-MPC) in the stomach. We compared 72 MPC cases with 160 non-MPC cases. Most gastric MPCs arose from tubular or papillary adenocarcinomas, and the proportion of MPC components ranged from 5% to 80%. MPCs were characterized by more frequent lymphovascular invasion and LN metastasis (P<0.0001), higher tumor node metastasis (TNM) stage (P=0.019), advanced age (>65 y; P<0.0001), and more frequent CD44v6 and aberrant ß-catenin expression (P<0.0001). The overall 5-year survival rates for patients with MPC were significantly worse than those with non-MPC (30% vs. 67%; P=0.002). Furthermore, when it was stratified by TNM stages, the survival rates were distinguished between MPC and non-MPC groups in TNM stages I to II (P=0.0003), but not in TNM stages III to IV. The presence of the MPC component was associated with a significantly worse patient survival by univariate (P=0.0003) and multivariate (P=0.04) analyses in patients with stages I to II gastric carcinoma. In conclusion, recognition of the MPC component in gastric carcinoma is critical, because the MPC component is associated with more frequent LN metastasis and a worse prognosis, especially in stages I to II gastric cancer.

Intraductal papillary mucininous neoplasm of the bile ducts: multimodality assessment with pathologic correlation.

Mucin-producing intraductal papillary neoplasm (adenocarcinoma/adenoma) in the bile duct is becoming recognized as a specific type of neoplasm. Since, it bears a striking similarity to intraductal papillary mucinous neoplasms of the pancreas with regard to its histopathologic features, the term "intraductal papillary mucinous neoplasms of the bile duct" (IPMN-B) is frequently used, although no definite terminology or definition has been decided by World Health Organization. This neoplasm lacks ovarian-like stroma and communicates with the bile ducts, unlike biliary mucinous cystic neoplasm (MCN). On the other hand, malignant IPMN-B is categorized as an intraductal-growth type of intrahepatic cholangiocarcinoma (ICC). In comparison to other types of ICC, such as the mass-forming type and periductal-infiltrating type that have poor resectability and an unfavorable prognosis, malignant IPMN-B can be resected and demonstrates a more favorable prognosis. Meanwhile, unlike biliary MCN that is usually confined in a closed cyst, IPMN-B can spread along the mucosal surface of the bile ducts, and it should be widely resected. Therefore, multimodality assessment is needed to ensure the correct diagnosis of IPMN-B. We herein review the imaging findings of IPMN-B with pathologic correlation.

Analysis of prognostic factors and a proposed new classification for invasive papillary mucinous neoplasms.

BACKGROUND: The characteristics of invasive type-intraductal papillary mucinous neoplasm (invasive IPMN) have not been fully explored due to limited reports. Furthermore, a straightforward method is needed to describe its aggressiveness. The purpose of this study was to investigate prognostic factors and to examine the clinical significance of percentage pancreatic volume occupied by the invasive component in invasive IPMN. METHODS: Of 217 patients who underwent surgical resection with a diagnosis of IPMN between 2001 and 2008, 41 had invasive IPMC. We serially sectioned pancreatic parenchyma at 5-7-mm intervals. Whole slides were reviewed by a pancreas-biliary tract special pathologist, who determined the percentage pancreatic volumes occupied by the invasive components (IC%) in whole IPMN lesions. RESULTS: By multivariate analysis, perineural invasion, metastasis, AJCC stage, and invasive component percentage (IC%) significantly predicted prognosis. IC% was found to be significantly associated with survival. Patients with an IC% <10 had a 3-year survival rate (YSR) of 100%, whereas patients with an IC% >50% had a 3 YSR of 36.5% and those with an IC% of 10-50% had a 3 YSR of 71.4% (p = 0.041). CONCLUSIONS: In addition to conventional prognostic factors, such as AJCC stage and perineural invasion, the percentage of pancreatic volume occupied by the invasive component (IC%) appears to be an important prognostic factor in invasive IPMN. The concept of IC% is straightforward, semiquantitative, and objective, and offers a means of determining tumor aggressiveness; hence, it could be a means of classifying invasive IPMN.

Establishment of an intraoperative staging system (iStage) by improving UICC TNM classification system for papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma generally has an indolent nature, but cases demonstrating certain features are progressive. UICC TNM classification is the most widely adopted system to evaluate the biological behavior of this carcinoma, but it is doubtful whether this system that evaluates only the preoperative findings can appropriately reflect patient prognosis. In this study, we established a new staging system (iStage) based on not only preoperative but also intraoperative findings. METHODS: We investigated the prognoses of 5,911 patients with papillary carcinoma without distant metastasis at diagnosis who underwent initial surgery between January 1987 and January 2005 and compared the utility of iStage with that of conventional classification systems, such as UICC Stage, MACIS score (>7 and ≤7), AMES, and CIH classification. RESULTS: Disease-free survival (DFS) and cause-specific survival (CSS) of patients with stage IVA were better than those of high-risk patients on other systems, and CSS of stage III patients did not differ from stage IVA patients. We established iStage by improving the original UICC stage. We set cutoff age to 55 years, instead of 45. Patients showing significant, not minimal, extrathyroid extension on intraoperative findings underwent T upgrading: tumor size 2 cm or smaller to T3 and larger than 2 cm to T4a. N classification was revised based on the size of node metastasis and extranodal tumor extension: N0, no preoperatively detected regional node metastasis; N1, preoperatively detected regional node metastasis measuring 3 cm or less and without extranodal tumor extension on intraoperative findings; N2, regional node metastasis >3 cm or having extranodal tumor extension on intraoperative examination. Five-year and 10-year DFS and CSS of iStage IVA patients were worse than high-risk patients on other classification systems, and iStage III patients showed a worse DFS, but not CSS, than iStage I or II patients. CONCLUSIONS: We established a new classification system, iStage, based not only on preoperative but also on intraoperative findings, which has high utility. Appropriate intraoperative evaluation is mandatory to grade biological characteristics, including prognosis, of papillary carcinoma.

Cystic papillary thyroid carcinoma in fine needle aspiration may represent a subset of the encapsulated variant in WHO classification.

This study audits the reliability of ultrasound-guided fine needle aspiration (FNA) in excluding papillary thyroid carcinoma (PTC) in thyroid cysts containing mural nodules, and investigates the histological counterpart of cystic PTC diagnosed on FNA. Using a 10-5 MHz ultrasound probe and a 27-gauge needle, solid portions of thyroid nodules were sampled and assessed immediately using both Diff-Quik and Ultrafast Papanicolaou stains. Unlike usual PTCs that demonstrate hypercellularity, the aspirates of cystic PTC showed low cellularity and consisted of papillae with atypical nuclei scattered in abundant thin colloid. Over a period of 13 years, histological follow-up was obtained from 11 women and 6 men in whom cystic PTC was reported on FNA. This represented 4.4% of 383 cases of PTC reported and 0.25% of all thyroid FNAs performed. In all 17 cases, histopathology showed encapsulated PTC in various stages of cystic degeneration. Sonography correlated well with histopathology, where findings ranged from cysts with small mural nodules to solid nodules with pockets of thin colloid. In 87 patients with thyroid cysts containing mural nodules, FNA findings were benign, as was clinical follow-up that ranged from 1 to 12 years. In conclusion, ultrasound-guided FNA, if performed in the manner described, can reliably distinguish cystic PTC from a benign cyst with a mural nodule. Cystic PTC on FNA in this series correlates to a subset of the encapsulated variant of PTC, an entity described in the 1988 WHO Histological Typing of Thyroid Tumours in the good prognostic category.

Problems and controversies in the histopathology of thyroid carcinomas of follicular cell origin.

CONTEXT: Despite past and recent efforts, many problems and controversies remain in the classification of thyroid carcinomas of follicular cell origin. These controversies have an impact on the prognosis and therapy of patients with thyroid carcinoma as well as on the development of robust cutting-edge research aimed at better outcome and quality of life. OBJECTIVE: To focus on 3 contentious areas with significant clinical value: the follicular variant of papillary thyroid carcinoma, the extent of invasion in follicular carcinoma, and the poorly differentiated thyroid carcinomas. DATA SOURCES: The published English language literature was reviewed. CONCLUSIONS: Recent data show that prognosis and therapy for many disease entities can be better delineated if a meticulous microscopic examination is performed. An accurate assessment of the extent of invasion (especially vascular) is crucial. Proliferative grading (ie, mitosis and necrosis) is of high prognostic value and should be looked for in every specimen. In addition, molecular data gathered to date can help reassess these tumors at the histologic level. Classification proposals based on personal experience rather than adequate and careful clinical follow-up should be discouraged.