Literature review and case report of bilateral intracystic papillary carcinoma associated with an invasive ductal carcinoma in a male breast.

Intracystic papillary carcinoma (IPC) is a rare tumor with good prognosis that occurs in only 5% to 7.5% of male breast cancer. We report a case of a 46-year-old man who presented a brown nipple discharge a few months ago. He had a bilateral IPC and an invasive ductal carcinoma on the right breast. A double mastectomy was then performed with a bilateral sentinel lymph node biopsy, and he received chemotherapy, radiotherapy, and hormonotherapy. Two years after the diagnosis, the patient recovered and was free of recurrence. Considering the scarcity of this tumor type, we conducted a systematic literature review on the PubMed of all the cases of IPC in men. The clinical presentation, imaging, and treatment of the 43 case reports from the 41 articles selected were described. Furthermore, no clear guidelines for IPC management are available. Conservative surgery should also be preferred, and a sentinel lymph node biopsy should be performed systematically. Moreover, radiotherapy should be proposed in the case of conservative surgery, and hormone therapy could be proposed in the case of invasive IPC or IPC associated with a ductal carcinoma in situ.

Comparative analysis of clinicopathologic characteristics and molecular subtypes of invasive papillary carcinoma of the breast and invasive ductal carcinoma: results from SEER database.

PURPOSE: To investigate the difference of clinicopathologic characteristics and prognosis between invasive papillary carcinoma (IPC) and invasive ductal carcinoma (IDC) in breast cancer patients, and to further confirm the influence of molecular subtype on prognosis of IPC. METHODS: A total of 158,132 eligible patients from 2010 to 2015 were identified from the Surveillance, Epidemiology, and End Results (SEER) database, of which 348 patients were IPC and 157,784 patients were IDC. We assessed the clinicopathologic characteristics, molecular subtypes and prognostic value of IPC and compared them with those of IDC. RESULTS: IPC was more frequently presented with older age at diagnosis, less proportion of married and white race, lower grade, smaller tumor size, higher rates of negative nodal status, more AJCC stage I disease and HR+/Her2- breast cancer, and was less likely to be treated with mastectomy, chemotherapy, and radiation therapy than IDC (p<0.05). IPC had a better 5-year breast cancer-specific survival (BCSS) and overall survival (OS) rates than IDC. After adjusting confounding and matching the confounding factors, IPC patients were still associated with better BCSS. Regarding patients with specific subtypes, patients with IPC had more HR+/Her2- subtypes. In addition, HR+/Her2--IPC patients had a better BCSS than HR+/Her2--IDC patients, but OS was similar between the two groups. However, BCSS and OS did not differ in the two groups after matching the confounding factors. Subgroup analysis indicated that molecular subtype may be the main confounding factor in IPC prognosis. CONCLUSIONS: IPC showed more favorable behavior than IDC, but prognosis was not as favorable as people once thought. The determination of the appropriate therapeutic regimen for IPC still needs to be made according to risk factors such as histological grade, pathological stage and molecular subtype.

Solid Papillary Carcinoma and Encapsulated Papillary Carcinoma of the Breast: Clinical-Pathologic Features and Basement Membrane Studies of 50 Cases.

INTRODUCTION: Solid papillary carcinoma (SPC) and encapsulated papillary carcinoma (EPC) of the breast are usually considered in situ lesions due to favorable prognosis, despite the variable presence of myoepithelial cells. We aimed to describe clinical-pathologic features including basement membrane (BM) studies in these tumors. METHODS: Patients diagnosed with SPC and EPC in 2000-2019 were retrospectively identified. Microscopic slides and clinical history were reviewed. Immunohistochemical stains for BM and myoepithelial markers were performed. RESULTS: Of 23 SPCs and 27 EPCs, there were 5/23 (21.7%) pure SPCs and 9/27 (33.3%) pure EPCs, while 4/23 (17.4%) and 12/27 (44.5%) were associated with ductal carcinoma in situ (DCIS), and 6/23 (26.1%) and 6/27 (22.2%) with invasive carcinoma, respectively; 8/23 (34.8%) SPCs were considered invasive. The median tumor size was 1.7 cm (range 0.1-16). All tumors were positive for hormone receptors and negative for HER2. Myoepithelial cells were absent in 20 tumors (40%) and focally present in 30 (60%). Collagen IV and laminin were negative in most invasive lesions, but they were expressed in 21/21 (100%) and 18/21 (85.7%) of EPCs without invasion, and 16/17 (94.1%) and 10/17 (58.8%) SPCs, including invasive SPCs, respectively. Lymph node involvement was identified in 3/26 (11.5%) patients, including micrometastasis in 1 EPC associated with DCIS, macrometastasis in 1 EPC associated with invasive carcinoma, and isolated tumor cells in 1 invasive SPC. Of 31 patients with outcome data (median follow-up 35 months, range 1-85), 2 (6.5%; 1 SPC, 1 EPC) developed local recurrence, both associated with invasive carcinoma. No distant recurrences or deaths were observed. CONCLUSIONS: Our study confirms favorable prognosis of SPCs and EPCs, with 2 local recurrences occurring in the presence of invasion. SPCs are more commonly associated with invasive carcinoma or considered invasive compared to EPCs (60.9 vs. 22.2%). The presence of BM material and lack of lymph node involvement in most cases indicates that the majority of these tumors may represent in situ lesions; however, some may behave as low-grade invasive malignancy with metastatic potential even in the absence of conventional invasion.

Papillary thyroid microcarcinomas: does subtyping predict aggressive clinical behavior?

The most common malignant neoplasm affecting the thyroid gland is papillary thyroid carcinoma (PTC). PTC can demonstrate a number of morphologic variants including, but not limited to, classic, follicular, and tall cell. Each of these morphologic subtypes carry distinct clinical characteristics such that certain variants, like tall cell, behave more aggressively than others. PTCs measuring less than or equal to 1.0 cm are classified as microcarcinomas. Although these lesions are thought to be clinically indolent, we hypothesized that, like their larger counterparts, certain histologic variants may lead to worse patient outcomes. To test our hypothesis, we analyzed our pathology archives between the years 2009 and 2020 for papillary thyroid microcarcinomas and assessed whether different morphologic features correlated with more aggressive clinical behavior. Our findings suggest that certain variants exhibit features that portend a more worrisome clinical course and thus papillary thyroid microcarcinomas should be subtyped to help predict patient outcome.

Reappraisal of pathological features of intraductal papillary neoplasm of bile duct with respect to the type 1 and 2 subclassifications.

The pathological spectrum of intraductal papillary neoplasm of bile duct (IPNB) remains to be clarified. A total of 186 IPNBs were pathologically examined using the type 1 and 2 subclassifications proposed by Japanese and Korean biliary pathologists incorporating a two-tiered grading system (low-grade and high-grade dysplasia), with reference to four subtypes (intestinal [i], gastric [g], pancreatobiliary [pb], and concocytic [o] subtype). IPNBs were classifiable into type 1 composed of low-grade dysplasia and 'high-grade dysplasia with regular structures' (69 IPNBs), and type 2 of 'high grade dysplasia with irregular structures and complicated lesions' (117 IPNBs). Type 1 was more common in the intrahepatic bile duct (78%), whereas type 2 was frequently located in the extrahepatic bile duct (58%). Mucin hypersecretion was more common in type 1 (61%) than in type 2 (37%). IPNBs were classifiable into the four subtypes: 86 iPNBs, 40 gIPNBs, 31 pbIPNBs, and 29 oIPNBs. The four subtypes were histologically evaluable with reference to the type 1 and 2 subclassifications. iIPNB and pbIPNBs were frequently classified as type 2, whereas types 1 and 2 were observed at similar rates in gIPNB and oIPNB. Stromal invasion was almost absent in type 1, irrespective of subtype, but was found in 66 of 117 type 2 IPNBs (P < .01), and postoperative outcome was favorable in IPNBs without invasion compared with IPNBs with invasion (P < .05). The type 1 and 2 subclassifications with reference to the four subtypes may provide useful information for understanding IPNB.

Ratio of maximum to minimum tumor diameter can predict the pathology type of renal cell carcinoma before surgery.

INTRODUCTION: Previous reports have described several methods and markers used to distinguish pathologic subtypes of renal cell carcinoma (RCC). This study aimed to evaluate the utility of the ratio of maximum to minimum tumor diameter (ROD) in predicting pathologic subtypes of RCC. METHODS: Data from patients with RCC who underwent surgery between January 2015 and December 2019 were reviewed retrospectively. The cutoff value for ROD was calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: In the clear cell RCC (ccRCC) and non-ccRCC groups, the optimal ROD cutoff value to predict ccRCC was determined to be 1.201 (sensitivity, 90.7%; specificity, 76.1%; area under the ROC curve [AUC], 0.827; p < 0.001). In the non-ccRCC group, the cutoff value for ROD in predicting papillary RCC was 1.092 (sensitivity, 87.9%; specificity, 40.5%; AUC, 0.637; p = 0.003). Compared with patients with ROD <1.201, more patients in the ccRCC group exhibited tumors with an ROD ⩾1.201 (14.2% versus 85.8%, respectively; p < 0.001). Multivariate analysis of preoperative features revealed that ROD ⩾1.201 was an independent predictive factor for ccRCC. In addition, patients with ROD ⩾1.201 had higher percentages of Fuhrman grade III/IV (91.2% versus 8.8%; p = 0.014), tumor necrosis (86.7% versus 13.3%; p = 0.012) and sarcomatoid differentiation (90.6% versus 9.4%; p < 0.001). CONCLUSIONS: ROD was a novel indicator for preoperatively predicting histologic type in patients with RCC. ROD cutoff values of 1.201 and 1.092 were the most discriminative for ccRCC and papillary RCC, respectively. Moreover, ROD ⩾1.201 was associated with high Fuhrman grade, sarcomatoid features, and tumor necrosis.

A comparison between unifocal papillary thyroid microcarcinoma with noninvasive follicular thyroid neoplasm with papillary-like nuclear features and other patterns: A retrospective clinicopathological study.

BACKGROUND: Papillary thyroid microcarcinoma (mPTC) is defined as a tumor with low malignancy potential. Different treatment protocols have been used at different centers for analyzing this tumor which has common recurrence and metastasis rates. Consequently, in 2016, the definition of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was accepted which included the lesions > cm. It is important to explain the clinical course and appropriate treatment options for mPTC and its subtypes. AIMS: In this study, we aimed to describe the clinical course of mPTC with and without NIFTP and to determine different risk groups among these subtypes. MATERIAL AND METHODS: We performed microscopic reexamination of about 280 unifocal mPTCs retrieved from our archives between 2007-2018 and analyzed the results of morphological and clinical comparison among these cases that had 0-11-years of clinical follow-up. RESULTS: Among 280 unifocal mPTCs, 127 cases (45.4%) had classical morphology, 58 (20.7%) had NIFTP, 53 (18.9%) had infiltrative pattern, 27 (9.6%) had oncocytic pattern, 12 (4.3%) showed capsular invasion, and 3 (1.1%) showed other morphologies. Seven patients were detected with lymph node metastasis and one with distant metastasis at diagnosis. Lymph node metastasis (recurrence) was postoperatively detected in five patients. All patients with recurrence were women. Moreover, three of these patients were in their 30s and two in 70s. The median diameter of the tumor was 3 mm. Both invasive and noninvasive cases have recurred. CONCLUSION: Contrary to the results of the previous studies, the results of our study did not confirm the indolent course of mPTC with NIFTP. However, metastasis was detected both at the time of diagnosis and during the postoperative period. The malignancy potential of these tumors may not be low. Therefore, more clinicopathological and molecular studies are needed to determine the biological behavior of mPTC cases with different histology.

Intraductal papillary neoplasm of the bile duct: Radiologic findings in a new disease. / Neoplasia papilar intraductal de la vía biliar: radiología en una nueva entidad.

Intraductal papillary neoplasm of the biliary tract (B-IPN) is a scarcely known entity in our daily practice due to its low prevalence. Until its new definition in the fourth edition of the WHO classification of the digestive tract tumors of 2010 the disease was grouped under a heterogeneous and imprecise terminology. In addition, in recent years there has been progress in the knowledge of its etiopathogenesis, its natural history and its findings in image. The purpose of this paper is to review these data underlining the radiological findings of the disease and its differential diagnosis.

Micropapillary urothelial carcinoma of urinary bladder displays immunophenotypic features of luminal and p53-like subtypes and is not a variant of adenocarcinoma.

OBJECTIVES: Micropapillary urothelial carcinoma of the urinary bladder (MPUC) is a rare variant of urothelial carcinoma which has aggressive clinical characteristics. The objective is to investigate the molecular subtypes of MPUC and the impact to the clinical outcome and determine whether MPUC represents a variant of adenocarcinoma. MATERIALS AND METHODS: We evaluated surrogate immunohistochemical markers of luminal, basal, and p53-like subtypes and correlated with prognosis and the expression of markers related to bladder adenocarcinoma and glandular differentiation in 56 cases of MPUC (10 cases of transurethral resection and 46 cases of radical cystectomy). Biomarker expression in co-existing conventional urothelial carcinoma was also analyzed. Cox regression analysis was performed to study the impact of molecular subtype on the clinical outcome. RESULTS: Thirty-four cases (61%) met criteria for the luminal subtype. Twenty-two cases (39%) displayed a p53-like subtype. In contrast, 40/56 (71%) cases of coexisting conventional urothelial carcinoma were classified as luminal subtype and 16/56 (29%) cases were designated as p53-like subtype. There was no significant survival difference between luminal subtype and p53-like subtype. CDX2, villin, and cadherin 17 were negative in all cases. MUC1 was strongly and diffusely expressed in the stroma-facing surface of MPUC tumor cells in all the cases. CONCLUSIONS: Our findings suggest that MPUC possesses characteristics of luminal and p53-like subtypes, and does not harbor phenotypic features of the basal subtype. There is no significant difference in the prognosis between luminal and p53-like subtype MPUC. MPUC is not a variant of adenocarcinoma and does not represent a form of glandular differentiation, in contrast to other organ sites.

The influence of papillary thyroid microcarcinomas size on the occurrence of lymph node metastases.

PURPOSE: Lymph node metastases (LNM) in papillary thyroid microcarcinomas (PTMC) are common. PTMC greater than 5 mm are considered to be more aggressive. Tumor greater than 5 mm is predictive factor for occurrence of LNM in PTMC, although there are insufficient data regarding this fact. The purpose of this study was to explore the relation between LNM and patients with small (≤5mm) and large (>5mm) PTMC. The second target was to determine the frequency of multifocality, bilaterality and capsular invasion in small and large PTMC, and their relation with LNM occurrence. METHODS: This study included 257 patients with PTMC. In all patients total thyroidectomy was performed, and lymph node checking of central and lateral neck region using sentinel lymph node (SLN) biopsy in clinically N0 patients, or modified radical neck dissection in clinically N1b patients or in case with positive SLN. RESULTS: LNM were detected in 33% of the patients, 27% in the central neck region and 20% in the lateral neck region with 6.23% of skip metastases. LNM were significantly frequent in large PTMC compared with small (46 vs 24%), in the central region (38 vs 19%) and the lateral region (28 vs 14%), with skip metastases 7.62% and 5.26%, respectively. Bilaterality and capsular invasion were frequent in large PTMC. Multifocality and male gander were predictive factors for LNM in small PTMC, while capsular invasion was the only predictive factor in large PTMC. CONCLUSIONS: Although LNM are frequent in large PTMC, the percentage of LNM is not negligible in small PTMC, especially if they are multifocal.

AJCC 7th edition staging classification is more applicable than AJCC 8th edition staging classification for invasive IPMN.

BACKGROUND: Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging systems have been introduced for pancreatic adenocarcinoma. However, the applicability of these classifications for invasive intraductal papillary mucinous neoplasms (IPMN) has not been systematically examined. METHODS: Patients with invasive IPMN were retrieved from a cohort of 18 geographical sites (1973-2014 varying) in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The 7th and 8th editions of the AJCC staging were compared. Survival rates and multivariate analyses were computed. RESULTS: In total, 1216 patients with resected invasive IPMN were included. A major difference between the 7th and 8th systems is the definition of stage IIA (7th, beyond the pancreas without involvement of major arteries; 8th, maximum tumor diameter > 4 cm). The hazard ratio (HR) of stage IIA disease (versus stage IA, HR = 2.33, P < 0.001) was higher than that of stage IB disease (HR = 1.48, P = 0.087) by the 7th edition classification, whereas the HR of stage IIA disease (HR = 1.26, P = 0.232) was even lower than that of stage IB disease (HR = 1.48, P = 0.040) by the 8th edition classification. In addition, for the 8th edition staging system, tumor size was not a predictor of survival in patients with resectable tumor > 2 cm (size > 4 cm versus > 2 ≤ 4 cm, HR = 0.91, P = 0.420). CONCLUSIONS: The AJCC 7th edition staging classification is more applicable than the 8th edition classification for invasive IPMN.

Is papillary thyroid microcarcinoma a biologically different disease? A propensity score-matched analysis.

BACKGROUND: Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary microcarcinoma is biologically different from larger papillary carcinoma >1 cm. METHODS: We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity-score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles. RESULTS: After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF-like vs RAS-like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix-associated pathways were enriched in the MSigDB database. CONCLUSION: Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.

Breast Tumours Resembling the Tall Cell Variant of Thyroid Papillary Carcinoma: Are They Part of the Papillary Carcinoma Spectrum or a Distinct Entity?

BACKGROUND: Papillary tumours of the breast are diagnostically challenging lesions and represent a wide spectrum of diseases from papilloma to invasive papillary carcinoma. A rare subtype of breast papillary tumour resembling the tall cell variant of thyroid papillary carcinoma (BTRTPC) has been described. The nomenclature of this entity, its relationship to other papillary tumours, and its nature, whether in situ or invasive, remain unclear. METHODS: Seventy-five papillary carcinomas (PCs) of the breast previously diagnosed in routine practice were reviewed and the presence of features (n = 10) characteristic of BTRTPC were assessed to determine whether BTRTPC comprises a distinct entity or is part of the spectrum of the previously defined PC variants. RESULTS: Nuclear overlapping and eosinophilic granular cytoplasm were seen in 81 and 75% of the cases, whereas nuclear grooves, nuclear clearing, and tall cells were noticed in 51, 42, and 38% of the cases, respectively; 27% of the cases showed macro- and micro-follicular architecture filled with colloid-like material. Five cases (7%) lacked oestrogen receptor (ER) expression. Co-existing invasive carcinoma was seen in 25 cases (33%). Two cases displayed several features characteristic of BTRTPC, and both were ER-negative. CONCLUSION: Features characteristic of BTRTPC overlap with other PCs of the breast. Molecular and immunohistochemical biomarkers are needed to provide objective diagnostic criteria for the characterisation of such lesions in routine practice.

Updates on the Genetics and Molecular Subtypes of Urothelial Carcinoma and Select Variants.

Urothelial carcinoma is a morphologically and genomically heterogeneous disease that exhibits a wide spectrum of morphologic features and molecular alterations and subtypes. Classic urothelial carcinoma (not otherwise specified) is the most common tumor type that develops in the urinary bladder but many, well-documented, variant histologies are commonly encountered in approximately one-third of invasive urothelial carcinoma, including squamous, glandular, micropapillary, sarcomatoid, small cell/neuroendocrine, clear cell, lymphoepithelioma-like, and plasmacytoid types, among others. In this review, we provide an update on the molecular advances in urothelial carcinoma and some of its variant histologies.

[Interpretation of the fourth edition of WHO pathological classification of the thyroid tumors in 2017].

In recent years, the incidence of thyroid carcinoma gradually increased in China. The pathology diagnosis and classification was based on WHO classification of Tumors of Endocrine Organs, the third edition which published in 2004. The fourth edition, WHO classification of Tumors of Endocrine Organs was published in July 2017. Compared with the third, some important aspects (or points) were revised: the ICD-O code of hyalinizing trabecular tumor was changed from 0 to 1; three other encapsulated follicular-patterned thyroid tumors were added; the variants of well differentiation thyroid carcinoma (including papillary carcinoma and follicular carcinoma ) which was originated from thyroid epithelial cells were updated; oncocytic cell tumors were separated from follicular tumors; the ICD-O code of ectopic thymoma was changed from 1 to 3. Refinement and standardization part of the concepts and diagnostic criterias were done which can solve practical problems in pathology diagnosis.

Papillary Thyroid Microcarcinoma: Reclassification to Non-Invasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features (NIFTP): a Retrospective Clinicopathologic Study.

Papillary thyroid microcarcinoma (PTMC) accounts for nearly 50% of newly diagnosed PTC cases. There is considerable debate in literature about the clinicopathologic features and prognostic significance of PTMC and whether it should be treated as a separate entity. Due to lack of agreement and supportive data, the consensus study group that established the criteria for non-invasive thyroid neoplasm with papillary-like features (NIFTP) kept its size above 1 cm i.e., excluding PTMC from this new group. As a result, to date, some patients diagnosed with PTMC get aggressive treatments such as partial or total thyroidectomy and even radioactive iodine ablation. We retrospectively studied clinicopathologic features and long-term follow-up of 48 cases of papillary thyroid microcarcinoma. Of these, 7 cases (15%) had capsular invasion, 2 cases (4%) had extrathyroidal extension, 1 case (2%) had lymphovascular invasion, 5 cases (25%) had lymph node metastases, no case (0%) had any distant metastases, and 1 case had recurrence after long-term follow-up (mean 13.7 years, range 1-21 years). Upon slide review, 8 cases fulfilled the criteria for NIFTP and were sub-classified under this new category. These 8 cases had no recurrence after long-term follow-up (mean 12.1 years, range 7-19 years). In this study, we confirmed the previous published reports exhibiting indolent nature of PTMC and also suggested that PTMC cases that fulfill all the criteria for NIFTP can be sub-classified under this term in order to avoid unnecessary aggressive treatment.

Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features: Can Cytology Face the Challenge of Diagnosis in the Light of the New Classification?

OBJECTIVES: To assess the cytological findings of noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), conventional papillary thyroid carcinomas (C-PTC), and invasive follicular variants of papillary thyroid carcinomas (IFV-PTC) to determine if there are cytological differences between groups. STUDY DESIGN: We have reviewed all thyroid fine-needle aspiration cytology samples diagnosed between 2000 and 2017. We have included all NIFTP cases (n = 6) and randomly selected cases of C-PTC (n = 14) and IFV-PTC (n = 8). RESULTS: Comparing NIFTP and C-PTC cases, NIFTP cases showed significantly less papillary or pseudopapillary architecture, more bidimensional groups and microfollicles, and less tridimensionality, giant cells, and nuclear folds. We observed a trend towards significance for smear cellularity and amount of cytoplasm. Presence of nuclear folds was the only significant difference between NIFTP and IFV-PTC cases. The differences between groups in percent papillary or pseudopapillary architecture, cellularity, and tridimensionality showed a trend towards significance. Amount of colloid, dirty background, pleomorphism or atypia, nuclear pseudoinclusions, type of chromatin, and nucleolus were not significant. CONCLUSIONS: No cytopathological feature can differentiate between invasive and encapsulated IFV-PTC. In accordance with the recently accepted category, PTC smears with cells arranged in a predominantly follicular architecture should be reported as Bethesda IV category with descriptive terms to avoid false-positive cases.

Recent Advances in the Classification of Low-grade Papillary-like Thyroid Neoplasms and Aggressive Papillary Thyroid Carcinomas: Evolution of Diagnostic Criteria.

Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas. Recognizing these differences becomes more important for the proper medical, surgical, and radiotherapeutic management of patients with these neoplasms.

Noninvasive Follicular Thyroid Neoplasms With Papillary-like Nuclear Features Are Genetically and Biologically Similar to Adenomatous Nodules and Distinct From Papillary Thyroid Carcinomas With Extensive Follicular Growth.

CONTEXT: - Proposed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs), formerly noninvasive encapsulated papillary carcinoma, follicular variant (PTC-FV), is an indolent tumor with follicular growth and frequent RAS mutations. OBJECTIVE: - To detect histologic and molecular differences separating NIFTP from follicular adenomas (FAs) and invasive carcinomas, particularly papillary carcinomas with extensive follicular growth (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV). DESIGN: - Sixty-one tumors were reviewed histologically and reclassified into 32 NIFTPs (52%), 4 IE-PTC-FVs (7%), 14 PTC-EFGs (23%), and 11 FAs (18%). Next-generation sequencing for mutations in 50 genes was performed. Clinical outcomes were recorded. RESULTS: - The NIFTPs and FAs were well circumscribed and unencapsulated. The FAs had bland nuclei, whereas the NIFTPs showed at least 2 of 3 (67%; sufficient) nuclear features (enlargement, irregular contours, chromatin clearing). The IE-PTC-FVs had follicular growth, sufficient nuclear features, and extensive capsular invasion. The PTC-EFGs had a median of 5% papillae with intrathyroidal invasion (broad-based, sclerotic, or small follicle growth patterns); intranuclear pseudoinclusions were present only in PTC-EFGs (9 of 14; 64%). Mutations included RAS in 20 of the 32 NIFTPs (62%), 4 of the 11 FAs (36%), and 3 of the 4 IE-PTC-FVs (75%); BRAF K601E in 1 NIFTP (3%); BRAF V600E in 5 PTC-EFGs (36%). No NIFTPs or FAs recurred or metastasized. All 4 IE-PTC-FVs (100%) had hematogenous metastasis. Two PTC-EFGs (14%) had lymphatic metastasis. CONCLUSIONS: - The morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports the genetic similarity of those follicular neoplasms in contrast to the unique presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria supported by molecular testing, tumors with extensive follicular growth can be classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus papillary type or BRAF V600E-like (PTC-EFG).