ࡱ > ` bjbjss .P e V d d d x |! |! |! 8 ! d " x \M " p$ " $ $ $ , , - L L L L L L L $ NN h P V M d / , @ , / / M $ $ M #: #: #: / < $ d $ J #: / L #: #: F h | d G $ " Zu |! 5 V G I ,M 0 \M /G Q S8 r Q G G b Q d UH - - h #: . T ]. - - - M M 9 ^ - - - \M / / / / x x x |! x x x |! x x x Tarik M. Elsheikh, MD
Director of Cytology
PA Labs, LLC
Ball Memorial Hospital
Muncie, IN.
Follicular Lesions of the Thyroid: Classification and Criteria
Introduction
Fine needle aspiration cytology (FNA) of the thyroid gland is primarily a screening test, but is also diagnostic in many conditions. Its main priority is not to miss too many cancers. High sensitivity, therefore, coupled with low false negative results is what most pathologists and clinicians stride towards achieving. Surgery for benign disease is well accepted by clinicians, as they understand that a major role of FNA is to provide a relative risk of malignancy, for the clinician and patient, on which they can base their management decision upon, i.e. surgery vs. watching. ADDIN EN.CITE Geisinger20048228226Geisinger,KRModern Cytopathology2004Philadelphia, PennsylvaniaChurchill Livingstone1 I will discuss, in this presentation, the differential diagnosis of follicular lesions, cytologic criteria, terminology recently suggested by the Papanicolaou society, classification, and clinical implications of various diagnostic entities.
Follicular lesions
Follicular lesions of the thyroid represent the most problematic area of thyroid FNA. The major entities included in the differential diagnosis are hyperplastic /adenomatoid nodule, follicular neoplasm (adenoma and carcinoma), and follicular variant of PTC.
Table 1: Differential diagnosis of Follicular lesionsHyperplastic/adenomatoid nodule
Follicular Neoplasm
Follicular adenoma
Follicular carcinoma
Follicular variant of Papillary carcinoma
In general, smears containing abundant colloid and few cells are more likely to be benign (zone I), whereas markedly cellular aspirates with scant or absent colloid are more likely to be neoplastic (zone II) [figure modified from Demay. Art & Science of Cytopathology, 1996].
SHAPE \* MERGEFORMAT
Some aspirates, however will show features that fall in the middle, sometimes refered to as the grey zone (zone II), i.e. moderate amount of colloid and moderate cellularity, and may be difficult to classify as either benign or neoplastic.
Interobserver variability
Several studies have examined the agreement in distinguishing follicular neoplasm (FN) from cellular hyperplastic nodule. ADDIN EN.CITE Clary2005919117Clary, K. M.Condel, J. L.Liu, Y.Johnson, D. R.Grzybicki, D. M.Raab, S. S.Department of Pathology, Allegheny General Hospital and University of Pittsburgh Medical Center Shadyside Hospital, Pittsburgh, Pennsylvania, USA. karen.clary@viahealth.orgInterobserver variability in the fine needle aspiration biopsy diagnosis of follicular lesions of the thyroid glandActa CytolActa Cytol378-82494Adenocarcinoma, Follicular/diagnosis/*pathologyAdolescentAdultAgedBiopsy, Fine-NeedleCarcinoma, Papillary/diagnosis/*pathologyCarcinoma, Papillary, Follicular/diagnosis/pathologyDiagnosis, DifferentialFemaleGoiter, Nodular/diagnosis/*pathologyHumansMaleMiddle AgedObserver VariationThyroid Neoplasms/diagnosis/*pathologyThyroiditis, Autoimmune/diagnosis/*pathology2005Jul-Aug16124165http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16124165 Stelow200583983917Stelow, E. B.Bardales, R. H.Crary, G. S.Gulbahce, H. E.Stanley, M. W.Savik, K.Pambuccian, S. E.Department of Pathology, University of Virginia, Charlottesville, USA.Interobserver variability in thyroid fine-needle aspiration interpretation of lesions showing predominantly colloid and follicular groupsAm J Clin PatholAm J Clin Pathol239-441242*Biopsy, Fine-NeedleComparative StudyDiagnosis, DifferentialHumansObserver VariationReproducibility of ResultsThyroid Diseases/*epidemiology/*pathology2005Aug16040295http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16040295 Yang200319519517Yang, G. C.Liebeskind, D.Messina, A. V.Department of Pathology, New York University School of Medicine, New York, New York, USA. grace.yang@nyu.eduShould cytopathologists stop reporting follicular neoplasms on fine-needle aspiration of the thyroid?CancerCancer69-74992Adenocarcinoma, Follicular/diagnosis/*pathology/surgeryAdultAgedBiopsy, NeedleFalse Positive ReactionsFemaleFollow-Up StudiesHumansMaleMiddle Aged*Neoplasm InvasivenessThyroid Diseases/diagnosis/*pathology/surgeryThyroid Neoplasms/diagnosis/*pathology/surgeryThyroidectomy2003Apr 2512704685http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12704685 2-4 Areas of greatest debate and confusion included the terminology and criteria employed in diagnosing FN. Differences in terminology involve mainly the use of 2 diagnostic categories (i.e. follicular lesion and FN) versus one category. Criteria for the diagnosis of FN varied from strict to none other than cellularity. For example, the proportion of microfollicles needed to establish a FN diagnosis varied from none to predominant. There was no clear definition of how cellular an aspirate needed to be in order to be classified as hypercellular. There were also major disagreements in recognizing colloid, especially when it had a watery-thin appearance.
Hyper plastic nodule
Hyper plastic nodule (HN) is characterized by the presence of abundant colloid and variable number of follicular cells. Often there is evidence of oncocytic metaplasia and degenerative changes including macrophages and old blood. The follicular cells are predominately arranged in flat sheets with a honeycomb configuration. The presence of few microfollicular structures is accepted. Occasionally, large balls and microtissue fragments are present, especially when larger gauge needles are used. The nuclei are uniform in appearance and approximate the size of RBCs. They show finely granular chromatin with rare small nucleoli. There is minimal nuclear overlapping and crowding. Colloid, when dense, is easy to recognize. It has a dark blue-violet-magenta appearance on Diff Quik stain, while stains dark green-orange with Papanicolaou (figure). Thin colloid has a blue-violet appearance on DQ, and light green-orange appearance on Pap stains. It often shows cracks and folds imparting a thin membrane or a crazy pavement look. Thin colloid, however, maybe difficult to recognize in Papanicolaou stained specimens and bloody specimens, where it can be easily confused with serum. It may also disappear completely in thin-layer preparations. ADDIN EN.CITE Biscotti199550150117Biscotti, C. V.Hollow, J. A.Toddy, S. M.Easley, K. A.Department of Anatomic Pathology, Cleveland Clinic Foundation, OH 44195, USA.ThinPrep versus conventional smear cytologic preparations in the analysis of thyroid fine-needle aspiration specimensAm J Clin PatholAm J Clin Pathol150-31042Biopsy, NeedleColloids/analysisEvaluation StudiesHistocytological Preparation Techniques/*standardsHumansThyroid Diseases/*diagnosis/physiopathologyThyroid Gland/chemistry/pathologyThyroid Neoplasms/chemistry/*diagnosis1995Aug7639188http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7639188 5
Follicular neoplasm
Using specific cytologic criteria, Kini et al. reported a 75% accuracy rate in the diagnosis of follicular carcinoma (FC) ADDIN EN.CITE Kini198582982917Kini, S. R.Miller, J. M.Hamburger, J. I.Smith-Purslow, M. J.Cytopathology of follicular lesions of the thyroid glandDiagn CytopatholDiagn Cytopathol123-3212Adenocarcinoma/pathologyAdenoma/pathologyBiopsy, NeedleCarcinoma, Papillary/pathologyCytodiagnosisDiagnosis, DifferentialGoiter, Nodular/pathologyHumansThyroid Diseases/*pathologyThyroid Neoplasms/*pathologyThyroiditis, Autoimmune/pathology1985Apr-Jun3841772http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3841772 6 Most other studies, however, could not reproduce such accuracy. ADDIN EN.CITE Rout199980180117Rout, P.Shariff, S.Department of Pathology, St John's National Academy of Health Sciences, Bangalore, India.Diagnostic value of qualitative and quantitative variables in thyroid lesionsCytopathologyCytopathology171-9103Adenocarcinoma, Follicular/*pathologyAdenoma/*pathologyBiopsy, Needle/methodsCarcinoma, Papillary/*pathologyChromatin/pathologyDiagnosis, DifferentialGoiter, Nodular/pathologyHumansNuclear Envelope/pathologyObserver VariationThyroid Neoplasms/*pathologyThyroiditis, Autoimmune/pathologyThyrotoxicosis/pathology1999Jun10390065http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10390065 7 In our opinion, and those of most experts in the cytology field, FNA can not distinguish between follicular adenoma and follicular carcinoma. Histologic confirmation is needed in such cases in order to demonstrate the presence of capsular and /or vascular space invasion. There are, however, several cytologic features reported to be associated with increased cancer risk (40-60% cancer risk). These features include an increased nuclear size (at least twice the size of RBC), marked nuclear atypia including significant nuclear pleomorphism and irregularity, significant nuclear overlapping, and predominance of microfollicular structures (involving > 75% of thyroid clusters). ADDIN EN.CITE Barbaro200181381317Barbaro, D.Simi, U.Lopane, P.Pallini, S.Orsini, P.Piazza, F.Pasquini, C.Soriani, G.Sezione Endocrinologia e Diabetologia, Spedali Riuniti Viale Alfieri 37, ASL 6 Livorno, Italy.Thyroid nodules with microfollicular findings reported on fine-needle aspiration: invariably surgical treatment?Endocr PractEndocr Pract352-775Adenocarcinoma, Follicular/pathology/surgeryAdultAged*Biopsy, NeedleCarcinoma, Papillary, Follicular/pathology/surgeryCell Nucleus/pathologyCohort StudiesDiagnosis, DifferentialFemaleFrozen SectionsHumansMaleMiddle AgedThyroid Neoplasms/*pathology/*surgeryThyroid Nodule/*pathology/*surgery2001Sep-Oct11585370http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11585370 Ersoz200481881817Ersoz, C.Firat, P.Uguz, A.Kuzey, G. M.Department of Pathology and Cytology, Cukurova University School of Medicine, Adana, Turkey.Fine-needle aspiration cytology of solitary thyroid nodules: how far can we go in rendering differential cytologic diagnoses?CancerCancer302-71025AdultAged*Biopsy, Fine-NeedleComparative StudyDiagnosis, DifferentialFemaleHumansMaleMiddle AgedRetrospective StudiesSensitivity and SpecificityThyroid Nodule/*pathology/surgery2004Oct 2515376197http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15376197 Goldstein200282482417Goldstein, R. E.Netterville, J. L.Burkey, B.Johnson, J. E.Section of Surgical Sciences and the Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. richard.goldstein@mcmail.vanderbilt.eduImplications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodulesAnn SurgAnn Surg656-62; discussion 662-42355Adenocarcinoma, Follicular/epidemiology/*pathology/surgeryBiopsy, NeedleCarcinoma, Papillary, Follicular/epidemiology/*pathology/surgeryFemaleHumansIncidenceMaleMiddle AgedThyroid Gland/*pathologyThyroid Neoplasms/epidemiology/*pathology/surgeryThyroid Nodule/*pathology2002May11981211http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11981211 Yang200319519517Yang, G. C.Liebeskind, D.Messina, A. V.Department of Pathology, New York University School of Medicine, New York, New York, USA. grace.yang@nyu.eduShould cytopathologists stop reporting follicular neoplasms on fine-needle aspiration of the thyroid?CancerCancer69-74992Adenocarcinoma, Follicular/diagnosis/*pathology/surgeryAdultAgedBiopsy, NeedleFalse Positive ReactionsFemaleFollow-Up StudiesHumansMaleMiddle Aged*Neoplasm InvasivenessThyroid Diseases/diagnosis/*pathology/surgeryThyroid Neoplasms/diagnosis/*pathology/surgeryThyroidectomy2003Apr 2512704685http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12704685 Kellman200180280217Kellman, AThyroid cytologyThyroidThyroid271-2771120014, 8-11 It is important to emphasize, however, that the mere presence of microfollicles is not equated with neoplasia. In fact, studies have shown that microfollicles associated with no atypia had a low cancer risk (6%), and that microfollicles lacking nuclear overlap and mixed with abundant colloid had a 0% chance of harboring cancer.
From review of the literature, our proposed cytologic criteria for a specific diagnosis of follicular neoplasm include high cellularity and scant colloid. In addition, there is prominent microfollicular and/or syncytial arrangement, involving greater than 50-75% of the cellular groups. There is prominent nuclear overlapping and crowding of the follicular cells with noticeable uniform appearance. Significant nuclear atypia may or may not be present, and includes nuclear enlargement that is greater than twice the size of RBC, coarse and clumped chromatin and prominent enlarged nucleoli.
Challenges in the diagnosis of Hyperplastic/Adenomatoid nodule (HN)
Clearly, one of the most difficult problems in thyroid cytology is distinguishing HN with little colloid from FN with some colloid. ADDIN EN.CITE DeMay19968038036DeMay, R. M.The art and science of cytopathology1996ChicagoASCP Press12 As previously mentioned, the mere presence of microfollicles is not diagnostic of FN, as microfollicles may be focally seen in 5-10% of HN. Up to 30% of HNs are highly cellular, while 15-20% of cases show scant colloid. Although degenerative changes are often associated with HN, they may be found in up to 30% of FN. A definitive diagnosis of HN should not be made in the absence of colloid. ADDIN EN.CITE DeMay19968038036DeMay, R. M.The art and science of cytopathology1996ChicagoASCP PressGeisinger20048228226Geisinger,KRModern Cytopathology2004Philadelphia, PennsylvaniaChurchill LivingstoneHarach199160260217Harach, H. R.Saravia Day, E.Zusman, S. B.Pathology Service, Dr A Onativia, Endocrinology and Metabolism Hospital, Salta, Argentina.Occult papillary microcarcinoma of the thyroid--a potential pitfall of fine needle aspiration cytology?J Clin PatholJ Clin Pathol205-7443AdultBiopsy, NeedleCarcinoma, Papillary/diagnosis/*pathology/surgeryFemaleFollow-Up StudiesHumansThyroid Neoplasms/diagnosis/*pathology/surgery1991Mar2013621http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2013621 Basu199281481417Basu, D.Jayaram, G.Department of Pathology, Maulana Azad Medical College, New Delhi, India.A logistic model for thyroid lesionsDiagn CytopatholDiagn Cytopathol23-781Adenocarcinoma/pathology/ultrastructureBiopsy, NeedleCarcinoma, Papillary/pathology/ultrastructureColloidsGoiter/pathologyGraves' Disease/pathologyHumansLogistic ModelsMultivariate AnalysisRegression AnalysisThyroid Diseases/*pathologyThyroid Neoplasms/pathology/ultrastructure19921551363http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1551363 1, 12-14
Challenges in the diagnosis of Follicular Neoplasm
Low cellularity may be encountered in aspirates of FN due to poor biopsy technique, or due to macrofollicular architecture, yielding prominent colloid and scant follicular cells. Some FN may also be highly vascular, yielding abundant blood with rare follicular groups showing prominent nuclear overlapping and/or microfollicular structures. ADDIN EN.CITE Yang200319519517Yang, G. C.Liebeskind, D.Messina, A. V.Department of Pathology, New York University School of Medicine, New York, New York, USA. grace.yang@nyu.eduShould cytopathologists stop reporting follicular neoplasms on fine-needle aspiration of the thyroid?CancerCancer69-74992Adenocarcinoma, Follicular/diagnosis/*pathology/surgeryAdultAgedBiopsy, NeedleFalse Positive ReactionsFemaleFollow-Up StudiesHumansMaleMiddle Aged*Neoplasm InvasivenessThyroid Diseases/diagnosis/*pathology/surgeryThyroid Neoplasms/diagnosis/*pathology/surgeryThyroidectomy2003Apr 2512704685http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12704685 4
PSC Approach to Grey Zone and Terminology
Although the terms Follicular Lesion and Follicular Neoplasm are used interchangeably by some authors, we do not consider them synonymous. According to literature review, lesions categorized as indeterminate account for 5 to 42% of FNA diagnoses. We do not recommend the use of Indeterminate as a stand alone diagnosis, as its meaning has not been standardized, and may be interpreted in different ways. Indeterminate has been used by different authors and institutions to refer to a variety of diagnoses including FN, follicular lesion, suspicious for malignancy, and atypia not otherwise specified. Redman et al. surveyed 133 clinicians (Endocrinologists, Surgeons, Thyroid specialists), in order to determine the implications of FNA diagnoses on management options. ADDIN EN.CITE Redman2006181817Redman, R.Yoder, B. J.Massoll, N. A.Department of Pathology, University of Florida College of Medicine, Gainesville, Florida.Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologistsThyroidThyroid1003-816102006Oct17042686http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17042686 15 Clinicians opted for repeat FNA in 98% of the responses, when the cytologic terminology was Non-diagnostic. Suspicious diagnoses elicited a 96% surgical excision response. Clinicians, on the other hand, chose repeat FNA (58%) and surgery (32%) for Indeterminate diagnoses. They selected repeat FNA (37%) and surgery (52%) for Atypical designations. ADDIN EN.CITE Redman2006181817Redman, R.Yoder, B. J.Massoll, N. A.Department of Pathology, University of Florida College of Medicine, Gainesville, Florida.Perceptions of diagnostic terminology and cytopathologic reporting of fine-needle aspiration biopsies of thyroid nodules: a survey of clinicians and pathologistsThyroidThyroid1003-816102006Oct17042686http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17042686 15 This study clearly demonstrated that confusion arose with Atypical and Indeterminate diagnoses. Indeterminate was confused with non-diagnostic in some cases, and Atypical was too ambiguous and treated as Suspicious in many cases. The majority of clinicians, on the other hand, correctly interpreted Non-diagnostic and Suspicious diagnoses.
Follicular Lesions and Terminology
Two European studies found no malignancies on followup of FNAs diagnosed as FL and FN. ADDIN EN.CITE Piromalli199283183117Piromalli, D.Martelli, G.Del Prato, I.Collini, P.Pilotti, S.Division of Diagnostic Oncology and Outpatient Clinic, Istituto Nazionale Tumori, Milan, Italy.The role of fine needle aspiration in the diagnosis of thyroid nodules: analysis of 795 consecutive casesJ Surg OncolJ Surg Oncol247-50504Adenoma/diagnosis/pathology/surgeryAdolescentAdultAgedAged, 80 and overBiopsy, NeedleCarcinoma, Papillary/diagnosis/pathology/surgeryChildComparative StudyFalse Negative ReactionsFalse Positive ReactionsFemaleFollow-Up StudiesHumansMaleMiddle AgedSensitivity and SpecificityThyroid Neoplasms/*diagnosis/pathology/surgeryThyroid Nodule/*diagnosis/pathology/surgeryThyroiditis/diagnosis/pathology/surgery1992Aug1640709http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1640709 16 ADDIN EN.CITE Foppiani200382082017Foppiani, L.Tancredi, M.Ansaldo, G. L.Ceppa, P.Auriati, L.Torre, G. C.Minuto, F.Giusti, M.DiSEM, DiCMI, University of Genova, Genova, Italy.Absence of histological malignancy in a patient cohort with follicular lesions on fine-needle aspirationJ Endocrinol InvestJ Endocrinol Invest29-34261Adenoma/epidemiology/*pathologyAdultAged*Biopsy, NeedleCarcinoma/epidemiology/*pathologyCohort StudiesDiagnosis, DifferentialFemaleGoiter, Nodular/pathologyHumansIncidenceItaly/epidemiologyMaleMiddle AgedThyroid Neoplasms/epidemiology/*pathology2003Jan12602531http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12602531 17 The authors advocated a less aggressive approach to management, i.e. clinical followup. FN, however, was loosely defined in these studies as hypercellular smears associated with scant colloid, and presence of microfollicles. There was no mention of percentage of microfollicle formation, nuclear features of follicular cells, or other architectural patterns. Permissiveness in applying strict criteria to the diagnosis of FN can lead to significant reduction of malignancy rate on followup. Cytologic features such as architecture and nuclear atypia, in addition to colloid and cellularity, should be incorporated into our criteria, in order to better define and classify those lesions falling in the grey zone. The utilization of more strict criteria can help shrink the grey zone further, resulting in less number of cases classified as indeterminate.
Cellular lesion can not rule out FN
In USCAP 2006, the Papanicolaou Society of cytopathology introduced the terminology of Cellular lesion can not rule out FN, in dealing with lesions falling in the grey zone. This terminology was chosen in order to stay away from the confusing terms of follicular lesion, indeterminate, atypical, etc. This designation is employed when the major differential diagnosis is hyperplasic nodule vs. FN. These aspirates are often highly cellular with scant colloid. There is admixture of flat sheets and microfollicles/syncytial fragments. Minimal nuclear overlapping and crowding may be present. This diagnosis is also rendered when smears from different passes show mixed cytologic findings ranging from benign to possible FN. Bloody specimens of low cellularity, but containing microfollicles and prominent nuclear overlap (highly vascular lesions) would also be included in this category.
Follicular variant of papillary carcinoma (FVPC)
These aspirates mainly display branching monolayered sheets, which is considered to be a significant low power discriminating feature from follicular neoplasms. ADDIN EN.CITE Fulciniti200182182117Fulciniti, F.Benincasa, G.Vetrani, A.Palombini, L.Dipartimento di Scienze Biomorfologiche e Funzionali, Sezione di Anatomia Patologica e Citopatologia, Facolta di Medicina e Chirurgia, Universita degli Studi di Napoli Federico II, Naples, Italy.Follicular variant of papillary carcinoma: cytologic findings on FNAB samples-experience with 16 casesDiagn CytopatholDiagn Cytopathol86-93252AdultAgedBiopsy, NeedleCarcinoma, Papillary/*pathologyChildFemaleHumansMaleMiddle AgedThyroid Neoplasms/*pathology2001Aug11477710http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11477710 18 Occasionally, there is predominance of microfollicles similar to follicular neoplasm, but appreciation of the nuclear features of PTC will usually establish the diagnosis of FVPC in most cases. Not infrequently, FVPC may show abundant colloid or paucity of nuclear features of PTC, leading to a false negative diagnosis of benign thyroid disease or follicular neoplasm. As a matter of fact, FVPC is only second to sampling error as the most common cause of false negative diagnoses in thyroid FNA. Wu et al. reported 11 false negative cases of FVPC, where 6 cases were attributed to sampling error (micropapillary carcinoma), and 5 cases showed focal atypia in a background of abundant colloid and cystic change. ADDIN EN.CITE Wu2006666617Wu, H. H.Jones, J. N.Osman, J.Department of Pathology, Ball Memorial Hospital, Muncie, IN 47303, USA. hhjwu@palab.comFine-needle aspiration cytology of the thyroid: ten years experience in a community teaching hospitalDiagn CytopatholDiagn Cytopathol93-6342AdultAgedBiopsy, Fine-NeedleFalse Negative ReactionsFemale*Hospitals, Community*Hospitals, TeachingHumansMaleMiddle AgedThyroid Diseases/*diagnosis/*pathologyThyroid Gland/*pathologyTime Factors2006Feb16514671http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16514671 19
Suspicious for PTC
We issue a diagnosis of suspicious for PTC when focal nuclear features of PTC, such as focal nuclear grooves associated with nuclear enlargement and powdery chromatin, are appreciated in an aspirate. The combination of flat syncytial sheets, nuclear enlargement, and fine powdery chromatin, was found to be the most sensitive, whereas the combination of nuclear enlargement, fine chromatin and nuclear grooves was found to be the most specific, in establishing the diagnosis of FVPC. ADDIN EN.CITE Wu200384184117Wu, H. H.Jones, J. N.Grzybicki, D. M.Elsheikh, T. M.Ball Memorial Hospital, Muncie, Indiana 47303, USA. wuh@palab.comSensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsyDiagn CytopatholDiagn Cytopathol262-6295Biopsy, Fine-NeedleCarcinoma, Papillary/pathologyCarcinoma, Papillary, Follicular/*diagnosisDiagnosis, DifferentialHumansThyroid Neoplasms/*diagnosis2003Nov14595792http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14595792 20 Intranuclear psuedoinclusions are seen in less than half of FVPC cases. ADDIN EN.CITE Wu200384184117Wu, H. H.Jones, J. N.Grzybicki, D. M.Elsheikh, T. M.Ball Memorial Hospital, Muncie, Indiana 47303, USA. wuh@palab.comSensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsyDiagn CytopatholDiagn Cytopathol262-6295Biopsy, Fine-NeedleCarcinoma, Papillary/pathologyCarcinoma, Papillary, Follicular/*diagnosisDiagnosis, DifferentialHumansThyroid Neoplasms/*diagnosis2003Nov14595792http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14595792 20 It is important to recognize suspicious for PTC as a distinct category, and not to lump it with other indeterminate or follicular neoplasm diagnoses, because of its substantially greater association with malignancy on surgical followup. Logani et al. and Wu et al. reported cancer followup rates of 77% and 75%, respectively, when rendering such diagnoses. ADDIN EN.CITE Logani200127027017Logani, S.Osei, S. Y.LiVolsi, V. A.Baloch, Z. W.Fine-needle aspiration of follicular variant of papillary carcinoma in a hyperfunctioning thyroid noduleDiagn CytopatholDiagn Cytopathol80-1251AdultBiopsy, NeedleCarcinoma, Papillary/*pathologyHumansMaleThyroid Nodule/*pathology2001Jul11466820http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11466820 Wu200384184117Wu, H. H.Jones, J. N.Grzybicki, D. M.Elsheikh, T. M.Ball Memorial Hospital, Muncie, Indiana 47303, USA. wuh@palab.comSensitive cytologic criteria for the identification of follicular variant of papillary thyroid carcinoma in fine-needle aspiration biopsyDiagn CytopatholDiagn Cytopathol262-6295Biopsy, Fine-NeedleCarcinoma, Papillary/pathologyCarcinoma, Papillary, Follicular/*diagnosisDiagnosis, DifferentialHumansThyroid Neoplasms/*diagnosis2003Nov14595792http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14595792 20, 21 This is in contrast to the cancer followup rate of 10-30% typically associated with indeterminate or follicular neoplasm diagnoses. With such an increased risk of malignancy, clinicians and patients may consider total thyroidectomy as another option, in place of lobectomy. Another management choice includes lobectomy with intra-operative consult, which has been shown to be helpful in additional 30% of cases. ADDIN EN.CITE Baloch200281181117Baloch, Z. W.Fleisher, S.LiVolsi, V. A.Gupta, P. K.Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. baloch@mail.med.upenn.eduDiagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytologyDiagn CytopatholDiagn Cytopathol41-4261Adenoma, Oxyphilic/*pathology/surgeryAdultAge DistributionAgedAged, 80 and overBiopsy, NeedleCarcinoma, Medullary/*pathology/surgeryCarcinoma, Papillary, Follicular/*pathology/surgeryDiagnosis, DifferentialFemaleGoiter, Nodular/pathologyHumansMaleMiddle AgedRetrospective StudiesSex DistributionThyroid Gland/*pathology/surgeryThyroid Nodule/*pathology/surgeryThyroiditis, Autoimmune/pathology2002Jan11782086http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11782086 22
Suspicious for malignancy
We use this category when the cytologic features are suggestive of a specific malignancy, but a definitive diagnosis can not be rendered. A definitive diagnosis of malignancy is often not rendered in these cases due to quantitative reasons ( i.e. malignant appearing cells, but limited cellularity) or qualitative reasons (i.e. focal or less than well developed features of malignancy, or an atypical lymphoid population). The most commonly encountered example of this diagnostic category is suspicious for PTC.
Diagnostic categories (as proposed by PSC)
Unsatisfactory
Benign, non-neoplastic
Cellular lesion, can not rule out follicular neoplasm
Follicular Neoplasm
Suspicious for malignancy
Malignant.
Clinical implications
The majority (70-80%) of FNAs classified as FN, are neoplastic on histologic followup. Using strict cytologic criteria, diagnoses of FN and cellular nodule can not rule out FN show cancer on histologic followup in 30% and 10% of cases, respectively. Using permissive criteria, however, and when FN and indeterminate diagnoses are combined, cancer is found in 20% of the cases. It is important, therefore, to separate FN as a distinct category from cellular hyperplastic nodule or other indeterminate follicular lesions. Most clinicians will recommend excision for FN, and accept the fact that the cytologic diagnosis is probabilistic and may be benign on followup. ADDIN EN.CITE Baloch200281181117Baloch, Z. W.Fleisher, S.LiVolsi, V. A.Gupta, P. K.Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA. baloch@mail.med.upenn.eduDiagnosis of "follicular neoplasm": a gray zone in thyroid fine-needle aspiration cytologyDiagn CytopatholDiagn Cytopathol41-4261Adenoma, Oxyphilic/*pathology/surgeryAdultAge DistributionAgedAged, 80 and overBiopsy, NeedleCarcinoma, Medullary/*pathology/surgeryCarcinoma, Papillary, Follicular/*pathology/surgeryDiagnosis, DifferentialFemaleGoiter, Nodular/pathologyHumansMaleMiddle AgedRetrospective StudiesSex DistributionThyroid Gland/*pathology/surgeryThyroid Nodule/*pathology/surgeryThyroiditis, Autoimmune/pathology2002Jan11782086http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11782086 Greaves200082582517Greaves, T. S.Olvera, M.Florentine, B. D.Raza, A. S.Cobb, C. J.Tsao-Wei, D. D.Groshen, S.Singer, P.Lopresti, J.Martin, S. E.Department of Pathology, Los Angeles County and University of Southern California Healthcare Network, Los Angeles 90033, USA.Follicular lesions of thyroid: a 5-year fine-needle aspiration experienceCancerCancer335-41906Adenocarcinoma, Follicular/*pathologyBiopsy, Needle/methodsFalse Negative ReactionsHumansObserver VariationResearch Support, U.S. Gov't, P.H.S.Retrospective StudiesSensitivity and SpecificityThyroid Diseases/*pathologyThyroid Neoplasms/*pathology2000Dec 2511156516http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11156516 Hamberger198276376317Hamberger, B.Gharib, H.Melton, L. J., 3rdGoellner, J. R.Zinsmeister, A. R.Fine-needle aspiration biopsy of thyroid nodules. Impact on thyroid practice and cost of careAm J MedAm J Med381-4733*Biopsy, NeedleCosts and Cost AnalysisCytodiagnosisFemaleHumansMaleMiddle AgedThyroid Diseases/*diagnosis/economics/pathology/surgeryThyroid Gland/*pathologyThyroid Neoplasms/*diagnosis/surgery1982Sep7124765http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7124765 La Rosa199160160117La Rosa, G. L.Belfiore, A.Giuffrida, D.Sicurella, C.Ippolito, O.Russo, G.Vigneri, R.Cattedra di Endocrinologia e Patologia Costituzionale, Ospedale Garibaldi, Catania, Italy.Evaluation of the fine needle aspiration biopsy in the preoperative selection of cold thyroid nodulesCancerCancer2137-41678Adenoma/pathologyBiopsy, NeedleCarcinoma/pathologyEvaluation StudiesHumansPredictive Value of TestsThyroid Diseases/*pathology/surgeryThyroid Neoplasms/pathology/secondary/surgery1991Apr 152004334http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2004334 22-25 Clinical followup or repeat FNA is recommended for those cases classified as cellular nodule can not rule out FN.
Assessment of probability of finding cancer on followup thyroidectomies
Wu et al Examined 401 FNAs with followup surgical excision, and calculated the cancer rates and risks associated with various cytologic diagnoses. Providing this data to clinicians and patients may be extremely helpful in deciding on management options.
FNA DiagnosisCancer RateCancer Risk*Benign non-neoplastic3 %--Cellular lesion, R/O FN14 %5 XFollicular neoplasm33 %11 XSuspicious56 %20 XMalignant100 %Inadequate/unsatisfactory12 %Cancer risk is compared to benign NN diagnosis
Thyroid FNA Diagnosis and management optionsDiagnosis Management optionsBenign
Followup
Cellular lesion, R/O FN
Followup
or
repeat FNA
Neoplasm
Excision / Lobectomy
Suspicious
Excision
Malignant
Excision
Unsatisfactory
Repeat FNA (US)
Summary
Thyroid FNA is primarily a screening tool, therefore, a conclusive diagnosis is not always required. A cytologists role is to minimize the number of indeterminate diagnoses without yielding unacceptable false negative and false positive rates. FNA can assign diagnostic probabilities that can help guide patient management in many cases. Although the utilization of these diagnostic categories is encouraged, they should not be used alone. Diagnoses should be qualified, when applicable, with an appropriate differential diagnosis. Individual centers should monitor their own diagnostic accuracy and cancer risks, and provide these data to their clinicians, to help guide their management. Recommendations for followup may be included in the report, if acceptable to clinicians. The use of the term Atypical or Indeterminate as a stand alone diagnosis is not recommended. Their meanings are not standardized and may be interpreted in different ways. Close cooperation between pathologists and clinicians is essential, so that the terminology used in the report and its clinical implications are clearly defined.
References
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