sparsely cellular specimen

Goellner et al. Some laboratories, for example, may want to state the risk of malignancy associated with the general category, based on their own data or that found in the literature (Table 2). One subcategory includes cases with a microfollicular pattern and minimal colloid, that is, follicular lesion of undetermined significance (FLUS). The diagnosis of this variant as a PTC is relatively easy, due to the numerous papillae and the coexisting intranuclear inclusions. Thyroid FNA is a well established procedure used in the preoperative diagnosis of thyroid nodules. Nuclear grooves become an important diagnostic feature when associated with an oval, enlarged nucleus with fine chromatin[41]. S The .gov means its official. (2021).Demystifying the Bone Marrow Biopsy: A Hematopathology Primer. . Lin Thyroid aspiration cytology: current status. As a result they may be not diagnosed through the FNA test, resulting in a false-negative test[44]. Management of a solitary thyroid nodule. Rubenfeld Touch preps can be imprinted, rolled, or crushed between glass to provide similar information. A full molecular panel of BRAF, RAS, RET/PTC and PAX8PPAR offer additional diagnostic value[58]. Q: Can your pathologist give you a preliminary assessment of the aspirate smear or flow cytometry analysis on the same day as a procedure if it was performed early in the morning? Yang The management of each case derives from the category that is classified. B However, there are cases with diagnostic uncertainty due to suboptimal sampling or preservation, and overlapping cytomorphologic features with other thyroid conditions. In several countries the Cytological Communities have adopted the first system or the other, as there is still an ongoing dispute on whether the 5-tiered system or the 6-tiered system is more efficient[12]. Since it is a two-dimensional specimen and reveals cells in cut section, it is not ideal for assessment of dysplasia (a marrow aspirate is preferred), but it is extremely useful in identifying possible reasons for a dry tap (a term for when liquid marrow cannot be aspirated during the bone marrow procedure), since the architecture can show fibrosis, sheets of cohesive plasma cells, or metastatic tumor which could result in a dry tap. Some components are more useful for particular studies. LiVolsi Theoharis CG, Schofield KM, Hammers L, Udelsman R, Chhieng DC. et al. R Help . Cellularity may in part be due to the LBC technique in comparison with smears made after sedimentation, . ( a) In this sparsely cellular specimen, some of the cells had abundant cytoplasm and enlarged nuclei, some with prominent nucleoli. Because of its aggressive, infiltrative nature, patients with an undifferentiated carcinoma often require a tracheostomy as an emergency procedure. . Prognosis is dismal with a mean survival of 2.5 to 6 mo and an overall 5-year survival of 0% to 14%. Quick tip: Flow cytometry cannot be performed on the clot section after the clot has set and after fixation in formalin. Fadda Note extensive red blood cells in the background. Proposal of the SIAPEC-IAP Italian Consensus Working Group. Figure 6. The isolated cyst-lining cells in thyroid aspirates are often difficult to distinguish from PTC. A malignant thyroid FNA diagnosis accounts for 4%-8% of all thyroid FNAs, the majority of which are PTCs, and these patients will require thyroidectomy[53]. Fine-needle aspiration biopsy (FNAB) showed sparsely cellular smears with a finely granular background and groups of cells arranged in 3-dimensional clusters and papillary formation (Figure 2, arrow). One nucleus has an apparent intranuclear pseudoinclusion ( arrow ). This category is reserved for aspirates with borderline cellularity and is subdivided into two subcategories. In order to establish a standardized diagnostic terminology/classification system for reporting thyroid FNAC results, the National Cancer Institute (NCI) in the United States sponsored the NCI Thyroid FNA State of the Science Conference with a group of experts at Bethesda, MD, in October 2007[7]. Redman R, Yoder BJ, Massoll NA. The preparation of a "cell block" (a formalin-fixed, paraffin-embedded sediment of the urine sample) can be particularly useful because small pieces of tumor are often easier to evaluate with this preparation method. ES Goellner Until recently there were no uniform criteria for the various diagnostic categories in thyroid cytopathology. Yang J, Schnadig V, Logrono R, Wasserman PG. Despite the fact that not all PTC were detected by this panel, a positive molecular test helped to refine the FLUS cases into high-risk and low-risk categories[61]. There are several exceptions to the numeric requirement of benign follicular cells. Excision is considered for persistently ND/UNS nodules because about 10% prove to be malignant.13. These changes are not pathognomonic, as they are frequently detected in some PTCs, especially in the follicular variant, and in benign lesions as well, such as follicular adenomas. The four components of a routine bone marrow analysis. View an interactive bone marrow clot specimen online. official website and that any information you provide is encrypted Clark Such changes may represent atypical but benign cyst-lining cells, but a papillary carcinoma cannot be entirely excluded (ThinPrep, Papanicolaou stain). Flat sheets showing enlarged, pale nuclei with finely granular chromatin of a papillary Ca case ( 40 pap stain on ThinPrep slide) (diagnostic categories VI). Some categories have 2 alternative names; a consensus was not reached at the NCI conference on a single name for these categories. Regardless the staining method used, all slides with diagnostic material are used for the evaluation and clarification of each case. Baloch ZW, Cibas ES, Clark DP, Layfield LJ, Ljung BM, Pitman MB, Abati A. Some cases may present with diagnostic difficulty if the specimen consists mainly of necrotic debris or if the tumor is extremely sclerotic (the paucicellular variant)[40,53]. Aspirates where malignancy is suspected but cannot be determined due to: Overlapping cytological features with other thyroid lesions, Specimens suspicious for a follicular or Hrthle cell neoplasm (see, Specimens with a minor degree of atypia, primarily cytologic or architectural (see, Frozen section has limited utility for suspicious for malignancy nodules (, 55 year old man with colon cancer metastasis within a NIFTP which was cytologically suspected of PTC (, 58 year old woman with mammary analogue secretory carcinoma of the thyroid which was cytologically suspected of PTC (, 63 year old man with follicular variant of papillary thyroid carcinoma presenting as a toxic nodule which was cytologically suspected of follicular variant of PTC (, 63 year old woman with hyalinizing trabecular tumor which was cytologically suspected of hyalinizing trabecular tumor (, 71 year old man with mixed medullary and follicular cell carcinoma of the thyroid which was cytologically suspected of thyroid carcinoma (, Pattern A (patchy nuclear changes): moderate to high cellularity, nuclei showing enlargement, pallor, grooves, irregularity or molding but absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern B (incomplete nuclear changes): nuclei showing enlargement with mild pallor and grooves, absence of nuclear irregularity, nuclear molding, nuclear pseudoinclusions, psammoma bodies and papillary architecture, Pattern C (sparsely cellular specimen): poor cellularity, presence of many findings suggesting papillary thyroid carcinoma, Pattern D (cystic degeneration): cystic degeneration based on foamy histiocytes, scattered clusters of follicular cells with the nuclei showing enlargement, pallor, grooves, absence of nuclear pseudoinclusions, psammoma bodies and papillary architecture, large, atypical, histiocytoid cells with enlarged nuclei and without abundant vacuolated cytoplasm (, Monomorphic population of isolated small or medium sized cells with a high nuclear cytoplasmic ratio, Nuclei are eccentrically located, with smudged chromatin, Numerous monomorphic small to intermediate sized lymphoid cells, Sparsely cellular and contains atypical lymphoid cells, Suspicious for malignancy, not otherwise specified, Other primary thyroid malignancies like anaplastic carcinoma and poorly differentiated carcinoma, Suboptimal cellularity or preservation can lead to uncertainty and result in a suspicious for malignancy interpretation, Usually surgical management similar to that of malignant nodules (, In suspicious for papillary thyroid carcinoma cases with low risk features ( 1 cm, without extrathyroidal extension and clinical metastasis), active surveillance is an option (, Molecular testing with high positive predictive value (, For suspicious for medullary thyroid carcinoma, Measuring serum calcitonin level or calcitonin immunostaining are recommended (, Repeat fine needle aspiration to obtain cells for flow cytometry (, A few follicular cells showing nuclear enlargement, pale and powdery chromatin and nuclear grooves are present, Correlation with serum calcitonin level or immunostaining might be helpful for definitive diagnosis if clinically indicated, Re-aspiration for flow cytometry might be helpful to better characterize the lymphocyte population if clinically indicated, Microfollicular architecture with minimal nuclear features of, Trabecular growth pattern of the cells with nuclear grooves and abundant nuclear pseudoinclusions, intratrabecular hyaline material, Nuclear changes of follicular cells with focal enlargement, grooves, prominent nucleoli and chromatin clearing in the lymphocytic background, An abundance of lymphocytes and plasma cells does not exclude the possibility of a coexisting, Numerous lymphocytes, few follicular cells, Elongated cells with pale chromatin, nuclear grooves and relatively large nucleoli, Spindle shaped morphology of the cell and nucleus, reminiscent of reparative epithelium in cervical Pap smears, Follicular variant of papillary thyroid carcinoma. These include hypocellular smears with extensive cystic degeneration with rare follicular cells with nuclear atypia indicative of PTC. Vimentin immunoexpression is also a common finding[52]. et al. Ghossein Loose cellular material can be held together to make into a cell block in all of the following EXCEPT a. agar b. albumin c. blood clot d. resin resin A slide of breast fluid has the cells washing off during staining. There are also sheets of follicular cells with large pale nuclei and some with nuclear grooves, but without intranuclear inclusions. Benign cyst-lining cells are typically polygonal or fusiform with abundant cytoplasm, well-defined cellular borders, sometimes enlarged, grooved nuclei, and small distinct nucleoli. Low and high power of clot particle. Papillary structures are not as common as it was believed, because intact papillae are often too large to enter the fine needle or are disrupted during the preparation of the smears. Contribution of molecular testing to thyroid fine-needle aspiration cytology of follicular lesion of undetermined significance/atypia of undetermined significance. Gupta Map ; Apps; Tools . The most common malignant diagnosis made after surgery in cases initially classified as AUS/FLUS is PTC, usually of the follicular variant (PTC-FV)[24,25]. The authors of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) recommended that the DC III (AUS/FLUS) category should not exceed 7% of the thyroid FNA diagnoses, and the risk of malignancy in this category should be in the range of 5% to 15%[23]. V 2. The terms for reporting results should have an implied (or explicit) risk of malignancy on which recommendations for patient management (eg, annual follow-up, repeated FNA, surgical lobectomy, near total thyroidectomy) can be based. The first draft of the committees summary documents was posted on the Web site and open for online discussion from May 1 to June 30, 2007. . If resected, virtually all benign follicular nodules turn out to be nodules of a multinodular goiter or follicular adenomas. They can be readily classified as malignant due to nuclear pleomorphism, chromatin clumping, necrosis, atypical mitoses and other malignant features[40]. L The thyroid nodules are aspirated 3 to 5 times with a 22-gauge or 25-gauge needle. Employing genetic markers to improve diagnosis of thyroid tumor fine needle biopsy. The Bethesda thyroid fine-needle aspiration classification system: year 1 at an academic institution. Kinematic comparison between the knee after bicruciate stabilized total knee arthroplasty and the native knee: A cadaveric study. The risk of malignancy in the HCLUS category was significantly lower than in the other subtypes of AUS. The high sensitivity rate, as well as the high negative prognostic value of BRAF testing in AUS/FLUS and SFN/SFN categories have been also demonstrated by Alexander et al[57]. Broome JT, Solorzano CC. The neoplastic cells resemble Hurthle cells but have diagnostic nuclear features of PTC. For a thyroid FNA specimen to be satisfactory for evaluation (and benign), 6 . Thyroid nodules is a very usual clinical problem, as it is diagnosed in approximately 60% of the general population in Western countries[1]. Descriptive comments that follow are used to subclassify the benign interpretation. and transmitted securely. Additional benign findings (eg, black thyroid, reactive changes, radiation changes, cyst lining cells) can be mentioned as descriptive diagnoses at the discretion of the cytopathologist. ID It was apparent from the discussions at the conference and the Web postings that the primary purpose of terminology is clarity of communication. Fine-needle aspiration cytology (FNAC) has been widely adopted as a meticulous, secure and cost-effective method for the diagnosis of non-toxic thyroid nodules[1,2]. Herein lies everything you were afraid to ask. Bethesda, MD 20894, Web Policies Extensive research is going on in this field; an important step for the introduction of new molecular markers in the diagnosis of molecular tumors could be the clinical testing of FNA samples in large multicenter trials. Cyst lining cells are usually elongated, containing pale chromatin, with sparsely found intranuclear grooves, large nucleoli, and always associated with hemosiderin-laden macrophages and benign-appearing macrofollicle fragments. However, this requires additional FNA passes or residual cellular material from the cytologic sample. While there are advantages and disadvantages to each component regarding turnaround time, comprehensiveness, and diagnostic utility (Table), their synergism provides ample information for your consultant hematopathologists. Therefore, in the majority of patients in the AUS/FLUS category (72%-80%) the diagnosis will be resolved by repeat FNA, although 20%-28% of them will have AUS/FLUS on the repeat aspirate and thus require surgery. Before the routine use of thyroid FNA, the percentage of surgically resected thyroid nodules that were malignant was 14%.1 With current thyroid FNA practice, the percentage of resected nodules that are malignant surpasses 50%.2. A: Probably, yes. The cytological diagnosis of PTC is based mainly on the characteristic nuclear morphology. Hematoxylin-eosinstained sections of the clot particle. BRAF mutation has become a specific marker for PTC and its variants[54]. A benign follicular nodule is the most common benign pattern that is, an adequately cellular specimen composed of varying proportions of colloid and benign follicular cells arranged as macrofollicle and macrofollicle fragments. Crowded macrofollicles with mild irregularities in nuclear membrane and prominent nucleoli in a specimen with scant colloid ( 40 pap stain on ThinPrep slide) (diagnostic categories III). In this study the AUS category was further subdivided into HCLUS (atypical cells rule out Hurthle cell neoplasm) and FLUS. Core tip: Fine-needle aspiration (FNA) cytology is widely used for the diagnosis of thyroid nodules, although cases with indeterminate results are not rare. These indeterminate aspirates may present with architectural atypia or nuclear atypia[21]. The 2-day live conference in October 2007, attended by 154 registrants including pathologists, endocrinologists, surgeons, and radiologists, gave the committees an in-depth opportunity to present their conclusions and debate controversial areas. Johnson Conspicuous cellularity alone does not qualify the nodule for a suspicious interpretation.23 If the sample is cellular but mostly macrofollicular (intact spheres and flat fragments of evenly spaced follicular cells), a benign interpretation is appropriate. The Bethesda System For Reporting Thyroid Cytopathology. J sharing sensitive information, make sure youre on a federal Why do some investigations yield more, or less, information than others? Correspondence to: Evangelos P Misiakos, MD, FACS, Associate Professor of Surgery, Attikon University Hospital, University of Athens School of Medicine, 76 Aigeou Pelagous Street, Agia Paraskevi, 15 341, Attica, 12462 Athens, Greece. Without the bone marrow matrix, these slides contain only cells directly from the marrow and can be stained and assessed both for lineage and cytologic morphology, with high correlations to what may be seen on aspirate and biopsy. Chemotherapy or radiotherapy usually cannot change the dismal prognosis of this cancer. A review of the English literature was conducted, and data were analyzed and summarized and integrated from the authors perspective. Lloyd "Demystifying the Bone Marrow Biopsy: A Hematopathology Primer." et al. Asa et al. These cells constitute more than 50% of tumor volume[44]. The National Cancer Institute Thyroid fine needle aspiration state of the science conference: a summation. Hamberger Nayar R, Ivanovic M. The indeterminate thyroid fine-needle aspiration: experience from an academic center using terminology similar to that proposed in the 2007 National Cancer Institute Thyroid Fine Needle Aspiration State of the Science Conference. The use of molecular markers can further increase the diagnostic value of FNA samples for the detection of thyroid cancer. JR Gross specimen was measuring about 2x2x1.5 cm in size, soft in consistency, brownish black in color and roughly oval in shape [Table/Fig-4]. In: Clark DP, Faquin WC, editors. Benign follicular nodules often have a small population of microfollicles and crowded groups. Those that are resected represent a selected population of patients with repeated AUS results or patients with worrisome clinical or sonographic findings. An online atlas of illustrations of the Bethesda diagnostic categories is currently being assembled on the Papanicolaou Society Website under the direction of Syed Ali, MD, chair of the Online Atlas Committee. CR Should atypical follicular cells in thyroid fine-needle aspirates be subclassified? Goellner ES ES (iii) Cytologic and architectural atypia: For most cases surgical resection is not an effective treatment and only palliative therapies are used. Adequacy issues usually arise in sparsely cellular specimens, since low cellularity or inadequate representation may pose potential for missing a significant pathological process including malignancy. This PTC variant is a circumscribed thyroid tumor with papillary architecture and lymphoid follicles that mimics a Warthin tumor of the parotid gland. LiVolsi qA;`Yb]@b,@ "~Xbqs8J In the World Health Organization classification, Hrthle cell adenoma and Hrthle cell carcinoma are considered oncocytic variants of FA and FC, respectively.24 Studies suggest, however, that follicular and Hrthle cell tumors have different underlying genetics.4,25 For this reason, and because they have such distinctive morphologic features, it is helpful to specify that a sample raises the possibility of a Hrthle cell rather than a follicular neoplasm. PU Deveci Cibas Figure 4. This category also includes cases with a predominant population of Hurthle cells; these cases are labelled Hurthle cell neoplasm (Figure (Figure3).3). Papaparaskeva K, Nagel H, Droese M. Cytologic diagnosis of medullary carcinoma of the thyroid gland. AS Note the trabecular bone (*) with trilineage hematopoiesis including megakaryocytes, granulocytic precursors, and erythroid islands presented in 2D following formalin fixation and paraffin processing. For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. As with the Bethesda System for cervical cytology, it is expected that subsequent workshops will lead to further refinements to this framework. Horn RC. Hematopathologists can assess morphology, histologic architecture, and immunologic and phenotype profiles (Figure 2) across all four components to create a comprehensive report for your patient. This system also contains guidelines for the diagnosis and treatment of indeterminate or suspicious for malignancy cases. Unless specified as ND/UNS, the FNA specimen is considered adequate for evaluation. BRAF mutation detection in indeterminate thyroid cytology specimens: underlying cytologic, molecular, and pathologic characteristics of papillary thyroid carcinoma. This conference established the Bethesda System for Reporting Thyroid Cytopathology (BSRTC), a 6-tiered diagnostic classification system based on a probabilistic approach[8,9]. The nuclear chromatin is similar to that seen in other neuroendocrine tumors, i.e., salt and pepper type (Figure (Figure7).7). Dottorini There is a predominance of Hrthle cells in a sparsely cellular aspirate with scant colloid. If the tumor is small and confined to the thyroid, thyroidectomy may be feasible; however, in most cases the tumor extends outside the thyroid gland preventing adequate resection[35]. Baloch ZW, LiVolsi VA. Fine-needle aspiration of thyroid nodules: past, present, and future. The specimen is usually cellular with polygonal cells in loose papillary clusters with abundant eosinophilic cytoplasm. The main difference between the 5-tiered system and the 6-tiered system is that the DC III [atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)] category is included only in the 6-tier system, a category with considerable prevalence, as it is calculated 6%-7% according to various statistics[14]. Interestingly all predicted cancer proved to be papillary thyroid carcinoma in the final histology[59]. Sparsely definition, in a thinly distributed way; not thickly or densely: Michigan's Upper Peninsula is very sparsely populated, as more than 90% of it is forested. Moreover, large, atypical, histiocytoid cells with enlarged nuclei and abundant vacuolated cytoplasm usually coexist. Report of the Thyroid Cancer Guidelines Update Group. The nucleoli are usually small and eccentric; however, rare oncocytic variants of PTC can show prominent nucleoli. A: Ideally, no. Rossi RT This category refers to cellular specimens with abundant follicular cells arranged in a microfollicular pattern with minimal colloid. In this pattern many features of PTC are found, but it is sparsely cellular. As a two-dimensional section of islands of preserved marrow content, the same stains applied to the core biopsy can be applied to the clot sections. H M Agarwal A, Kocjan G. FNAC thyroid reporting categories: value of using the British Thyroid Association (Thy 1 to Thy 5) thyroid FNAC reporting guidelines. The Bethesda System for Reporting Thyroid cytopathology. Diagnostic terminology for reporting thyroid fine needle aspiration cytology: European Federation of Cytology Societies thyroid working party symposium, Lisbon 2009. Fine-needle aspiration in the work-up of thyroid nodules. Cytologic preparations typically have high cellularity, and colloid is scant or absent. et al. This variant is sometimes difficult to diagnose, because in some cases the characteristic neoplastic cells are sparsely evident in the mass. This distinction cannot be made by FNA and is of no consequence to the patient. How does one separate cellular follicular lesions of the thyroid by fine-needle aspiration biopsy? There was also a great difference regarding the percentage of the cases classified into the TIR 2/ DC II (benign) category (83.9%) compared with approximately half (55.4%) of the cases in the 6-tiered system. ED DP et al. Royal College of Physicians. Bethesda guidelines suspicious for malignancy, Ali: The Bethesda System for Reporting Thyroid Cytopathology - Definitions, Criteria and Explanatory Notes, 2nd Edition, 2018, Head Neck Pathol 2019 Oct 17 [Epub ahead of print], Noninvasive follicular thyroid neoplasm with papillary-like nuclear features, invasive follicular variant of papillary thyroid carcinoma, Bethesda category V suspicious for malignancy (SM) is used when some cytologic features are strongly suspected of malignancy but are not sufficient for a conclusive diagnosis (, Higher suspicion of malignancy than atypia of undetermined significance / follicular lesion of undetermined significance (AUS / FLUS) but lower suspicion than malignant, Molecular testing with mutation panels may be useful, particularly for potential noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) cases, Purpose of separating suspicious for malignancy from malignant is to preserve the very high positive predictive value of the malignant category without compromising the overall sensitivity of fine needle cytology aspiration, Used when cytology is strongly suspected of malignancy but is not sufficient for a conclusive diagnosis, Frequency < 5%, resection rate 70%, risk of malignancy 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant), Most common histological diagnosis is papillary thyroid carcinoma (PTC) (, Risk of malignancy: 80% (NIFTP = malignant), 45 - 60% (NIFTP malignant) (, Suspicious for malignancy interpretation allows for more conservative management options (e.g. The bone marrow aspirate is arguably the most straightforward aspect of the bone marrow workup. The Paris System for Reporting Urinary Cytology tried lately to address adequacy. Nuclear atypia or pleomorphism and mitoses are uncommon. Extra smeared slides are kept unstained for possible subsequent ancillary staining (e.g., MPO, PAS, esterases). (General, Ortho . Agrawal S, Rao RS, Parikh DM, Parikh HK, Borges AM, Sampat MB. Bongiovanni M, Crippa S, Baloch Z, Piana S, Spitale A, Pagni F, Mazzucchelli L, Di Bella C, Faquin W. Comparison of 5-tiered and 6-tiered diagnostic systems for the reporting of thyroid cytopathology: a multi-institutional study. VA Thus, our aim was to standardize a manual, simple, cost-effective innovative technique, namely, ACS to process clear/sparsely cellular specimens and also to compare ACS smears along with cytocentrifuged specimens which were used as control smears. Each diagnostic category is associated with a specific risk of malignancy and a recommendation for management. For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with a general diagnostic category. Patients with the sporadic forms of MTC or the familial MTC are most often middle-aged (mean age 50 years old), except in familial cases, in which they are relatively younger. {t+[O-]:KtJE]+ZhoZo$ZfqemI,W69l]g]EuGnWMGow" elP~G>6?{LsTY?R+-jW:E#x( xtT} . The following breakdown shines some light inside the black box of hematologic diagnostics and may provide insight into what the hematopathology report tells you. JA The most common sites are the lungs, bone, liver and brain. In this review we analyze all literature regarding Thyroid Cytopathology Reporting systems trying to identify the most suitable methodology to use in clinical practice for the preoperative diagnosis of thyroid nodules. We reviewed the English literature regarding Thyroid Cytopathology systems in order to identify the most suitable methodology, taking into account our prospective as well. These alterations were made in order for the British system to be analogous to the BSRTC[11,16], although in other countries these modifications have not be totally embraced. In such laboratories, macrophages only often constituted the great majority of ND/UNS cases, with rates that ranged from 15% to 30%.2,9,11,12 Other laboratories considered the risk of a false-negative result negligible and reported macrophages only as benign.10,11 At the 2007 NCI Conference, it was decided that cyst-fluid-only (CFO) cases should be considered a clearly identified subset of ND/UNS.

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