Follicular dendritic cell sarcoma of the cervical lymph node diagnosed on fine needle aspiration cytology.

Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: An interobserver study of key cytomorphological features from a large academic medical centre.

OBJECTIVE: Because of the indolent nature of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) and potential requisite for a more conservative treatment, it is crucial to identify features of this entity preoperatively. Our group recently published findings that there are several cytomorphological features that may be used as clues to distinguish NIFTP, papillary thyroid carcinoma (PTC) and follicular adenoma (FA) on fine needle aspiration. Therefore, we aimed to determine the interobserver reproducibility of these findings. METHODS: Presurgical fine-needle aspiration slides from NIFTP (n = 30), classic PTC (n = 30) and FA (n = 30) collected from 1/2013-8/2016 were reviewed by seven cytopathologists blindly. Presence of selected cytomorphological features was recorded and compared to determine percent agreement and inter-rater reliability among study cytopathologists using Gwet's AC1 statistics. RESULTS: For all the cytomorphological features, the overall percent agreement amongst the pathologists ranged between 65.1% and 86.8% (Gwet's AC1 0.30-0.80). There was substantial or almost perfect agreement (Gwet's AC1 > 0.60) in seven cytomorphological features in the classic PTC group, in six features in the NIFTP group and in five features in the FA group. There were no features with poor agreement (Gwet's AC1 < 0.0). CONCLUSIONS: The current study supports the reproducibility of our previous findings. The high level of agreement amongst pathologists for these groups, and particularly the NIFTP group, supports the notion that when viewed in combination as a cytological profile, these cytomorphological features may assist the cytopathologist in raising the possibility of NIFTP preoperatively. This can potentially aid clinicians in deciding whether more conservative treatment may be appropriate.

Repeat Fine-Needle Aspiration With Molecular Analysis in Management of Indeterminate Thyroid Nodules.

OBJECTIVE: To analyze clinical outcomes in a series of indeterminate thyroid nodules (ITNs) with repeat fine-needle aspiration (FNA) biopsy and results of genomic classifier. STUDY DESIGN: Historical chart review. SETTING: Tertiary care center. METHODS: We reviewed FNA samples from subjects with Bethesda III or IV diagnoses from January 2015 to December 2018 at a single institution and selected those with repeat FNA and ThyroSeq testing of the same nodule. Patient demographics, Bethesda classifications, ThyroSeq results, treatment detail, and surgical pathology, when available, were analyzed. RESULTS: Ninety-six patients with cytologic diagnosis of ITN, repeat FNA, and ThyroSeq testing were identified. Following repeat FNA, 55 nodules (57%) remained ITN; 40 (42%) were reclassified as benign; and 1 (1%) was reclassified as suspicious for malignancy. In 31 patients with ThyroSeq analysis accompanying initial and repeat FNA, 26 (84%) had the same result on each, while 5 (16%) tested ThyroSeq positive following an initially negative result (κ = 0.24). Most nodules that were downgraded to Bethesda II on repeat FNA (37/40, 93%) were managed nonsurgically. Patients with ThyroSeq-positive results were treated with surgery more often (25/28, 89%) than patients with ThyroSeq-negative results (11/68, 16%; P < .0001). In excised nodules, the prevalence of malignancy and noninvasive follicular thyroid neoplasm with papillary-like nuclear features was 28% (n = 10) and 22% (n = 8), respectively, and all malignancies were low risk. CONCLUSION: In this case series, repeat FNA helped patients with ITNs avoid diagnostic surgery through reclassification to benign cytology. The risk of high-risk malignancy in ThyroSeq-positive nodules with repeat indeterminate cytology was low.

Predictive Value of a Genomic Classifier in Indeterminate Thyroid Nodules Based on Nodule Size.

Importance: Genomic classifiers were developed to better guide clinicians in the treatment of indeterminate thyroid nodules (ITNs). To our knowledge, whether there is variation in the diagnostic accuracy of these tests depending on ITN size has not been previously studied. Objective: To analyze the diagnostic performance of a genomic classifier in relation to ITN size. Design, Setting, and Participants: A case series study with medical records review was conducted including all patients with a cytologic diagnosis of ITN managed with genomic classifier testing and surgery from January 2015 to December 2018 at NYU Langone Health. Demographics, ITN characteristics, genomic profiles, treatment, and final pathologic findings were recorded. Data analysis was conducted from March to April 2021. Main Outcomes and Measures: The primary aim was to assess the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of a genomic classifier test (ThyroSeq) in relation to ITN size (<2, 2-4, and >4 cm). The secondary aim was to investigate the risk of cancer associated with genetic signatures. Results: Of the 212 patients with 218 ITNs, 158 (74.5%) were women; median (SD) age was 49 (15.6) years. Genomic classifier results were positive in 173 ITNs (79.4%) treated with surgery. In this group of 173 positive ITNs, 46 (26.6%) were malignant on final pathologic testing. Overall, the observed cancer prevalence in the population was 23.9% (52 ITNs). In 45 ITNs that underwent surgery despite a negative genomic classifier interpretation, 6 (13.3%) were malignant. The PPV of a positive test was 27% and the NPV was 87%. The PPV and NPV findings improved as the ITN size increased (<2 cm [n = 98]: PPV, 25%; NPV, 79% vs >4 cm [n = 33]: PPV, 50%; NPV, 89%). Test specificity was higher in larger ITNs (<2 cm: 15% vs >4 cm: 40%; P = .01). Isolated RAS sequence variations were the most common variant identified in malignant nodules (11 [21.1%] of all ITNs), followed by BRAF variants (7 [13.5%] of all ITNs). Conclusions and Relevance: In this case series, the performance of the ThyroSeq test improved for larger ITNs. The risk of cancer in large ITNs with negative test results was low. These data suggest that, in genomic classifier-negative ITNs larger than 4 cm, initial management of thyroid lobectomy may be sufficient.

Pattern recognition of benign nodules at ultrasound of the thyroid: which nodules can be left alone?

OBJECTIVE: The purpose of this study was to evaluate morphologic features predictive of benign thyroid nodules. MATERIALS AND METHODS: From a registry of the records of 1,232 fine-needle aspiration biopsies performed jointly by the cytology and radiology departments at a single institution between 2005 and 2007, the cases of 650 patients were identified for whom both a pathology report and ultrasound images were available. From the alphabetized list generated, the first 500 nodules were reviewed. We analyzed the accuracy of individual sonographic features and of 10 discrete recognizable morphologic patterns in the prediction of benign histologic findings. RESULTS: We found that grouping of thyroid nodules into reproducible patterns of morphology, or pattern recognition, rather than analysis of individual sonographic features, was extremely accurate in the identification of benign nodules. Four specific patterns were identified: spongiform configuration, cyst with colloid clot, giraffe pattern, and diffuse hyperechogenicity, which had a 100% specificity for benignity. In our series, identification of nodules with one of these four patterns could have obviated more than 60% of thyroid biopsies. CONCLUSION: Recognition of specific morphologic patterns is an accurate method of identifying benign thyroid nodules that do not require cytologic evaluation. Use of this approach may substantially decrease the number of unnecessary biopsy procedures.

Hürthle cell lesions on thyroid fine needle aspiration cytology: Molecular and histologic correlation.

BACKGROUND: Hürthle cell lesions often pose diagnostic challenges, despite their common occurrence on thyroid fine-needle aspiration cytology (FNAC). The associated molecular alterations are also not well understood. Therefore, our study aimed to delineate the molecular profile of Hürthle cell lesions classified as Bethesda Categories III or IV (atypia of undetermined significance (AUS) or suspicious for follicular neoplasm (SFN)) on FNAC and to correlate this molecular profile with surgical resection findings. METHODS: This study consisted of 188 Hürthle cell lesions with indeterminate cytology and ThyroSeq® v2/v3 molecular testing results. Surgical follow-up was available for 33 cases. RESULTS: The majority of indeterminate Hürthle cell lesions had negative ThyroSeq® results (61%) and were benign on available surgical follow-up. The most prevalent mutations involved the RAS gene (21%), which were associated with benign lesions, non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), and malignancy. The remaining mutations involved less than 18% of the cases, including PAX8/PPARG (3.7%), TSHR (3.7%), EIF1AX (2.7%), MET (2.1%), PTEN (1.6%), clonal copy number alteration (1.6%), TERT (1.1%), and 0.5% each of GNAS, PIK3CA, and TP53 mutations. On follow-up, 45% were benign, 24% were NIFTP, and 30% were malignant. The malignant cases had different molecular alterations. CONCLUSION: No single molecular alteration defines cytologically indeterminate Hürthle cell lesions; the majority of cases have low-risk or no molecular alterations and are benign on follow-up. These findings suggest that molecular testing may be useful, but is not definitive, in determining which cases may be managed conservatively; additional studies are needed to fully determine the negative predictive value in ruling out malignancy.

Distinguishing parathyroid and thyroid lesions on ultrasound-guided fine-needle aspiration: A correlation of clinical data, ancillary studies, and molecular analysis.

BACKGROUND: Differentiating parathyroid and thyroid lesions can be challenging because of considerable morphologic overlap and anatomic proximity. Therefore, the authors sought to identify characteristic morphologic patterns and useful adjunct tests to distinguish these 2 entities. METHODS: A search was conducted in the study institution database for clinically indeterminate thyroid nodules from 2000 through 2016 with an emphasis on confirmed parathyroid nodules. Pathology reports, slides, ancillary studies, molecular analysis, and clinical and radiologic data were retrieved. RESULTS: A total of 143 cases of clinically indeterminate thyroid nodules were identified; 34 of these were confirmed parathyroid nodules. Three cytologic patterns were identified: 1) oncocytic cell pattern (9 cases; 26%); 2) follicular lesion of undetermined significance-like/papillary-like pattern (14 cases; 41%); and 3) nonspecific endocrine cell clusters (11 cases; 32%). Bare oval nuclei (100%), nuclear overlap (88%), crowded sheets (88%), and intracytoplasmic vacuoles (62%) were observed. Ten cases (29%) demonstrated positive immunostaining for parathyroid hormone (PTH), 7 cases (21%) demonstrated a positive PTH assay, and 9 cases (26%) had PTH detected by ThyroSeq v.2. The remaining 8 cases were morphologically either indeterminate or suggestive of parathyroid origin. The cytologic diagnosis was confirmed clinically (20 cases) or surgically (14 cases). Based on cytology alone, 8 cases initially were diagnosed as thyroid tissue and amended to parathyroid lesion after ancillary studies were performed, including 5 cases based on ThyroSeq v.2 results alone. CONCLUSIONS: Lesions with follicular lesion of undetermined significance-like or oncocytic features are prone to misdiagnosis. The current study identified distinct cytologic patterns in parathyroid lesions suggestive of parathyroid origin, which, together with PTH immunostains or assay, molecular studies, or sestamibi scans, aid in distinguishing parathyroid from thyroid lesions. Cancer Cytopathol 2017;125:674-82. © 2017 American Cancer Society.

Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: Report of two cases and review of the literature.

Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.

Is an increase in CD4/CD8 T-cell ratio in lymph node fine needle aspiration helpful for diagnosing Hodgkin lymphoma? A study of 85 lymph node FNAs with increased CD4/CD8 ratio.

BACKGROUND: An elevated CD4/CD8 T-cell ratio on flow cytometry (FCM) analysis has been reported in the literature to be associated with Hodgkin lymphoma (HL). The purpose of our study was to determine the diagnostic significance of an elevated CD4/CD8 ratio in lymph node fine needle aspiration (FNA) specimens. DESIGN: Between 1996 and 2002, out of 837 lymph node FNAs submitted for flow cytometry analysis, 85 cases showed an elevated CD4/CD8 ratio, defined as greater than or equal to 4, without definitive evidence of a lymphoproliferative disorder. The cytologic diagnoses of these 85 cases were grouped into four categories: reactive, atypical, Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Histologic follow-up was available in 17/85 (20%) of the cases. RESULTS: 5 of the 64 cases in which FCM and cytology did not reveal evidence of a lymphoproliferative disease had tissue follow-up because of persistent lymphadenopathy and high clinical suspicion. 3/5 (60%) confirmed the diagnosis of reactive lymphadenopathy. The two remaining cases (40%) were positive for lymphoma (1HL, 1NHL). 8/15 cases called atypical on cytology had histologic follow-up. 7/8 (87.5%) cases were positive for lymphoma (3HL, 4NHL). 3/4 cases called HL on cytology had tissue follow-up and all 3 (100%) confirmed the diagnosis of HL. One case diagnosed as NHL on cytology was found to be a diffuse large B-cell lymphoma. In summary, out of 17 cases with histologic follow-up 4/17 (24%) were reactive with CD4/CD8 T-cell ratio of 4.1-29, 7/17 (41%) were HLs with CD4/CD8 T-cell ratio of 5.3-11, and 6/17 (35%) were NHLs with CD4/CD8 T-cell ratio of 4.2-14. CONCLUSION: An elevated CD4/CD8 ratio on FCM is a nonspecific finding which may be seen in both reactive and lymphoproliferative disorders. The cytomorphologic features of the smear are more relevant than the sole flow cytometric finding of an elevated CD4/CD8 ratio.

Multiple system Erdheim-Chester disease with massive hypothalamic-sellar involvement and hypopituitarism.

Erdheim-Chester disease (ECD) is a rare multiple system histiocytosis that is characterized pathologically by xanthogranulomatous infiltrates and radiologically by symmetrical sclerosis of long bones. The diagnosis is often confirmed by biopsy of bone or of orbital or retroperitoneal soft tissue. Intracranial involvement is rare. The authors report a case of ECD in which the diagnosis was made after biopsy of a hypothalamic mass. The mass had been discovered during a workup for panhypopituitarism in a 55-year-old man with urological and bone disease. Aside from diabetes insipidus, other features of pituitary insufficiency have seldom been reported and no patients have presented with a hypothalamic tumor. The endocrinological and neurological aspects of ECD are discussed, as is its differential diagnosis. Reported cases of the disorder associated with hypopituitarism or found during biopsy of central nervous system structures are also reviewed.

Fractured colon: an endoscopically distinctive lesion associated with colonic perforation following colonoscopy in patients with collagenous colitis.

BACKGROUND: Collagenous colitis is characterized by collagen deposition in the superficial colonic mucosa, beneath the surface epithelium, resulting in chronic nonbloody diarrhea of variable severity. The mucosa generally appears endoscopically normal. METHODS: We report the occurrence of distinctive linear mucosal tears, unassociated with trauma, in 4 patients during diagnostic colonoscopy. The patients' tissue specimens were examined histologically, and clinical courses were recorded. OBSERVATIONS: Recognition of linear "fractures" was followed in 3 patients by colonic perforation. One patient required colectomy. Severe collagenous colitis was present in all. The resection specimen contained shallow linear ulcers overlying fibrotic submucosa, with pneumatosis and acute peritonitis. CONCLUSIONS: We theorize that the stiffness of the colon in areas of collagenous colitis with submucosal fibrosis makes it susceptible to linear "fractures" during colonoscopic air insufflation with subsequent transmural air dissection. We urge extreme caution if this lesion is recognized at colonoscopy and recommend aborting the examination and obtaining plain radiographs to detect free intraperitoneal air.

Malignant solitary fibrous tumor of the tongue.

Solitary fibrous tumor is a generally benign spindle-cell neoplasm that has been predominantly described in the visceral pleura and other serosal sites and is extremely rare in the head and neck area. We report the first known case of malignant solitary fibrous tumor of the tongue in a 57-year-old female patient who experienced rapid growth of a longstanding right anterior tongue mass, with associated dysphagia and dysarthria. Magnetic resonance imaging was suggestive of a low-flow vascular malformation not requiring preoperative embolization. The patient underwent partial peroral glossectomy for the excision of the tumor. Final pathology, however, was consistent with solitary fibrous tumor, characterized as malignant by histopathologic criteria, and the patient was returned for re-excision of the close surgical margins. The patient has experienced symptomatic improvement, and she remains free of recurrence 12 months later. All reports of solitary fibrous tumors of the oral cavity and 3 reports of the tongue tumors described in the literature to date represent benign lesions. To our knowledge, this is the first report of a malignant solitary fibrous tumor of the tongue. Presentation, differential diagnosis, criteria for malignancy, treatment, and possible prognostic implications of this rare entity are discussed.