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.

Nonimage-guided fine needle aspiration biopsy of palpable axillary lymph nodes in breast cancer patients.

We report the utility of office-based, nonimaged guided fine needle aspiration of palpable axillary lymph nodes in breast cancer patients. We examine the sensitivity and specificity of this procedure, and examine factors associated with a positive fine needle aspiration biopsy result. Although the utility of ultrasound-guided fine needle aspiration biopsy (FNA) of axillary lymph nodes is well established, there is little data on nonimage guided office-based FNA of palpable axillary lymphadenopathy. We investigated the sensitivity and specificity of nonimage-guided FNA of axillary lymphadenopathy in patients presenting with breast cancer, and report factors associated with a positive FNA result. Retrospective study of 94 patients who underwent office-based FNA of palpable axillary lymph nodes between 2004 and 2008 was conducted. Cytology results were compared with pathology after axillary sentinel node or lymph node dissection. Nonimage-guided axillary FNA was 86% sensitive and 100% specific. On univariate analysis, patients with positive FNA cytology had larger breast tumors (p = 0.007), more pathologic positive lymph nodes (p < 0.0001), and were more likely to present with a palpable breast mass (p = 0.006) or with radiographic lymphadenopathy (p = 0.002). FNA-positive patients had an increased presence of lymphovascular invasion (p = 0.001), higher stage of disease (p < 0.001), higher N stage (p < 0.0001), and higher rate of HER2/neu expression (p = 0.008). On multivariate analysis, radiographic lymphadenopathy (p = 0.03) and number of positive lymph nodes (p = 0.04) were associated with a positive FNA result. Nonimage-guided FNA of palpable axillary lymphadenopathy in breast cancer patients is an inexpensive, sensitive, and specific test. Prompt determination of lymph node positivity benefits select patients, permitting avoidance of axillary ultrasound, sentinel lymph node biopsy, or delay in receiving neoadjuvant therapy. This results in time and cost savings for the health care system, and expedites definitive management.

p16 immunostaining in fine-needle aspirations of the head and neck: determining the optimal positivity threshold in HPV-related squamous cell cancer.

INTRODUCTION: There is no consensus for interpretation of p16 immunohistochemistry (IHC) in cytology preparations. Our study aims to assess p16 IHC staining in formalin-fixed cytology cell blocks (CBs) from head and neck squamous cell carcinoma (HNSCC) fine-needle aspiration (FNA) specimens in comparison with surgical pathology p16 staining and to determine the reproducibility of p16 IHC scoring in CBs. METHODS: A total of 40 FNAs from 2014 to 2019 of HNSCC with p16 IHC were obtained. CB p16 staining was scored independently by 5 cytopathologists as interval percentages of tumor cell positivity. Receiver operating characteristic (ROC) curves were examined to determine optimal cutoffs for each pathologist based on sensitivity and specificity values. Gwet's coefficient (AC1) was calculated to assess inter-rater reliability. RESULTS: Greater than 10% was the lowest threshold to reach 100% specificity with high sensitivity (55%-84%) in all 5 raters. Rater performances were similar, with areas under the curve (AUCs) ranging from 0.89 to 0.95. Using the >10% threshold, Gwet's AC1 = 0.72 (95% CI: 0.56-0.89). Diagnostic performance improved further when low-cellularity cases were excluded, with AUC ranging from 0.94 to 0.99 and Gwet's AC1 = 0.79 (95% CI: 0.61-0.98). CONCLUSION: p16 IHC performed on cytology CBs can serve as a surrogate marker for the detection of HPV with high sensitivity and specificity levels. Using a threshold lower than that recommended for surgical pathology for the interpretation of p16 positivity may be appropriate for FNA cytology CB preparations. All cytopathologists in our study displayed reproducible high sensitivity and specificity values at the >10% threshold.

Diagnosis of Schistosoma haematobium on voided urine cytology: a case report with radiologic correlation.

BACKGROUND: Infection with schistosomal species is becoming a more frequent finding in hospitals throughout the United States. Some causes that can be attributed to the rise include increased immigration from and travel to endemic areas. CASE: We report a case of urinary schistosomiasis diagnosed on urine cytology in a 7-year-old Nigerian boy. Infection was suspected after review of the clinical history and correlation with radiologic images. CONCLUSION: The rise in incidence has made it necessary for cytopathologists to be increasingly aware of these infections, in particular, Schistosoma haematobium, because it is the most frequent agent to be encountered on a cytology specimen, particularly urine. Similar cases have been published, one with specimen concentration and one without. However, no cases of cytology diagnosis with radiologic correlation are seen in the English literature.

Encapsulated anaplastic thyroid carcinoma transformed from follicular carcinoma: a case report.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is rare but is one of the most aggressive and lethal human malignancies. Cytologically, ATC has a variable morphologic appearance, including squamoid, giant, spindled and pleomorphic cells. The coexistence of ATC and differentiated or poorly differentiated thyroid carcinoma has been described and usually is diagnosed when the disease is locally advanced. CASE: We describe a case of surgically resectable, encapsulated, well-circumscribed ATC occurring in association with a better differentiated follicular carcinoma diagnosed by fine needle aspiration in a patient exposed to external ionizing radiation. CONCLUSION: Encapsulated variants of anaplastic carcinoma can be seen in association with lower grade thyroid carcinoma such as follicular carcinoma. Accurate diagnosis is dependent on adequate sampling.

Origin, frequency and clinical significance of glandular cells in liquid-based pap tests from patients posthysterectomy.

OBJECTIVE: To quantify the frequency and significance of glandular cells in posthysterectomy liquid-based (SurePath, TriPath Imaging, Burlington, North Carolina, U.S.A.) vaginal Pap tests. STUDY DESIGN: The presence of benign glandular cells in vaginal Pap tests from posthysterectomy patients represents a diagnostic challenge and may pose management issues. We investigated the presence, frequency and significance of glandular cells in 52 liquid-based (SurePath) vaginal Pap tests from posthysterectomy patients by combining cytomorphologic findings with adjunctive immunohistochemistry and mucin stains performed on cell block preparations and correlated the findings with clinical data. RESULTS: After performing these special studies, the frequency of reporting glandular cells in posthysterectomy Pap tests decreased from 3.5% to 1.2% of all vaginal Pap tests performed in a 6-month period. CONCLUSION: A strong association of the presence of benign appearing glandular cells and a previous history of gynecological malignancy (71%) and chemotherapy/radiation (59%) were noted, likely representing a regenerative process in response to injury or therapy.

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.

Diagnosis of myeloid sarcoma involving salivary glands by fine-needle aspiration cytology and flow cytometry: report of four cases.

Myeloid sarcoma involving salivary glands is extremely rare. Here, we report four cases of this rare occurrence, diagnosed by fine-needle aspiration biopsy. All of four patients had previous diagnoses of myeloid neoplasms. They presented with a solitary mass in the parotid or submandibular salivary gland. The cytological evaluation of the aspirates revealed scattered salivary gland acini admixed with dispersed atypical cells. In three cases, the atypical cells appeared to be heterogeneous, intermediate to large in size, and have folded nuclei with fine chromatin. In another case the atypical cells were monotonous and had round nuclei with fine chromatin. The myeloid lineage of the atypical cells was demonstrated by flow cytometric analysis. High clinical suspicion, careful cytological evaluation, and concurrent ancillary studies are essential for establishing a diagnosis of myeloid sarcoma.

Lasting pathologic complete response to chemotherapy for ovarian cancer after receiving antimalarials for dermatomyositis.

Could hydroxychloroquine and quinacrine antimalarial therapy for dermatomyositis later attributed to a paraneoplasic manifestation of an ovarian cancer enhance its subsequent response to chemotherapy? Five months after being diagnosed with dermatomyositis, while somewhat improved with hydroxychloroquine, quinacrine and methotrexate, this 63-year-old woman presented with an advanced intra-abdominal epithelial ovarian cancer documented (but not resected) at laparotomy. Neoadjuvant carboplatin/paclitaxel resulted in remarkable improvement of symptoms, tumour markers and imaging findings leading to thorough cytoreductive surgery at completion of five cycles. No tumour was found in the resected omentum, gynaecologic organs, as well as hepatic and nodal sampling thus documenting a complete pathologic response; a subcutaneous port and an intraperitoneal (IP) catheter were placed for two cycles of IP cisplatin consolidation. She remains free of disease 3 years after such treatment and her dermatomyositis is in remission in the absence of any treatment. We discuss a possible role of autophagy in promoting tumour cell survival and chemoresistance that is potentially reversed by antimalarial drugs. Thus, chemotherapy following their use may subsequently lead to dramatic potentiation of anticancer treatment.

Intraparenchymal leiomyoma of the breast: a case report and review of the literature.

We report a case of an intraparenchymal leiomyoma of the breast with description of the radiologic, histopathologic, and immunohistochemical findings. To the best of our knowledge, this is the first case of an intraparenchymal leiomyoma of the breast diagnosed by core needle biopsy and the 22nd case described in the literature. In addition, we review the literature on this uncommon breast neoplasm.

Pulmonary metastasis of giant cell tumor of the bone diagnosed by fine-needle aspiration biopsy.

Giant cell tumor is a benign but locally aggressive tumor that primarily affects the epiphyses of long bones of young adults. Pulmonary metastases in giant cell tumor are rare (about 1-9%). Here, we report a case of metastatic pulmonary giant cell tumor in a patient who had a previous history of giant cell tumor of the distal femur with multiple recurrences. The diagnosis of pulmonary metastasis was achieved by cytologic evaluation with concurrent immunohistochemical studies in material obtained by fine-needle aspiration biopsy. The aspirate smears contained clustered and dispersed mononuclear and osteoclast-like giant cells that had bland nuclei with inconspicuous nucleoli. All multinucleated cells showed immunoreactivity to KP-1 antibody, a histiocytic marker (not lineage specific) and only a subset of mononuclear cells (30%) stained with this marker. Twenty percent of the mononuclear cells also displayed increased Ki-67 and p53 protein expression. The pulmonary metastasis was similar morphologically and immunophenotypically to the recurrent giant cell tumor of the bone.

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.

Metastatic carcinoid tumor to the breast: report of two cases and review of the literature.

The breast is an unusual site for carcinoid metastasis. Due to increasing survival rates for carcinoid tumors, however, awareness of their rare complications is important. Carcinoid metastasis to the breast typically presents as a palpable breast mass or a mass on screening mammogram. Because imaging findings are nonspecific, the diagnosis is established through histological findings of neuroendocrine features corresponding with the known primary carcinoid pathology. Correctly distinguishing metastatic carcinoid from primary breast carcinoma is crucial to avoid more invasive procedures required for the latter. Two cases of metastatic carcinoid to the breast are presented with review of the literature.

Management issues in breast lesions diagnosed by fine-needle aspiration and percutaneous core breast biopsy.

The use offine-needle aspiration biopsy or percutaneous core needle biopsy to diagnose breast lesions has increased during the past few decades. Although the benefits of these procedures are well known, controversies remain about the management of certain categories of breast lesions detected by these methods. This article discusses the management issues in categories of breast lesions, including papillary lesions, atypical lobular hyperplasia and lobular carcinoma in situ, and mucinous lesions diagnosed by the preoperative techniques of aspiration or core biopsy.

CDX-2 expression in pulmonary fine-needle aspiration specimens: a useful adjunct for the diagnosis of metastatic colorectal adenocarcinoma.

CDX-2 is a homeobox gene, which encodes a transcription factor that plays a vital role in the development and differentiation of intestinal epithelial cells. Recent studies showed that CDX-2 protein expression by immunohistochemistry (IHC) has a high predictive value for confirming the diagnosis of colorectal adenocarcinoma (ACA). The differentiation of primary pulmonary ACA from metastatic colorectal ACA can be extremely challenging on fine-needle aspiration (FNA). The results of immunostains for TTF-1, CK 7, and CK 20 may be controversial in the differential diagnosis. In this study, we evaluated the clinical utility of CDX-2 in lung FNA specimens. Cell blocks from 41 primary lung and 20 colorectal ACAs metastatic to the lungs were retrieved. Cell block sections were immunostained with a CDX-2 monoclonal antibody. Sensitivity and specificity of CDX-2 for colorectal ACA was 75 and 100%, respectively. All five cases negative for CDX-2 were moderately to poorly differentiated colorectal ACAs. Our study confirms that CDX-2 is a highly useful immunohistochemical marker for the differentiation of primary pulmonary ACA from colorectal ACA metastatic to the lungs in FNA specimens. Of diagnostic importance is the loss of CDX-2 immunoreactivity in poorly differentiated colorectal ACAs.

Fine-needle aspiration biopsy for the primary diagnosis of lymphoproliferative disorders involving the spleen: one institution's experience and review of the literature.

We report the fine-needle aspiration (FNA) biopsy findings for the primary diagnosis of lymphoproliferative disorders involving the spleen. We analyzed six cases of primary diagnosed lymphoma involving the spleen and out of these cases, identified one case of primary splenic lymphoma. We explore the potential pitfalls and difficulties encountered in making a primary diagnosis of lymphoma involving the spleen and how the preparation of the specimen for flow cytometric studies and/or cell block for immunohistochemical analysis can greatly aid in making a definitive diagnosis. To the best of our knowledge, this is the first report of T-cell rich B-cell subtype of diffuse large B-cell lymphoma and only the second report of primary splenic lymphoma of the spleen diagnosed by FNA biopsy. An extensive review and analysis of the literature involving FNA biopsy of the spleen is also discussed.

Fine-needle aspiration biopsy findings in epithelioid myoepithelioma of the parotid gland: a case report.

We describe the fine-needle aspiration biopsy findings in a case of epithelioid myoepithelioma of the parotid gland in a 24-yr-old male. The cytologic features of myoepithelioma of the parotid gland are only documented in a few case reports and we believe the cytologic description of the epithelioid variant has been described in only one other case. The differential diagnosis with other salivary gland neoplasms is discussed.

Primary intravascular synovial sarcoma: a disease of young adult women? Report of a case diagnosed by aspiration biopsy and review of the literature.

Intravascular synovial sarcoma (IVSS) is an extremely rare tumor with only four well-documented cases in the English literature. All tumors were located in large veins of the lower extremities or trunk in young women except for one case occurring in a 54-yr-old woman. We report here an additional case of IVSS arising from the superior vena cava in a 32-yr-old woman who presented with a cervical mass and superior vena cava syndrome. A fine-needle aspiration biopsy (FNAB) was performed and showed a malignant biphasic tumor with spindle cell and epithelioid components. The tumor cells were negative for CD31, CD34, factor VIII, desmin, smooth muscle actin, and S-100 protein, and had positive staining for vimentin and cytokeratin (AE1/AE3) predominantly in the spindle and epithelial components, respectively. A diagnosis of synovial sarcoma was made and confirmed in a subsequent transvascular biopsy demonstrating chromosomal translocation t(X, 18) by fluorescence in situ hybridization using a dual color, break-apart-style probe for SYT. Although clinically similar to previously reported IVSS, this is the first case arising in large veins of the upper portion of the trunk and diagnosed by FNAB.

Effect of Bethesda 2001 on reporting of atypical squamous cells (ASC) with special emphasis on atypical squamous cells-cannot rule out high grade (ASC-H).

We compared the overall ASC rate and the outcomes for women with different categories of ASC before and after TBS 2001 to evaluate the impact of TBS 2001. Our laboratory reported ASC in four subcategories before TBS 2001; ASC, favor reactive (ASC-R), favor low-grade squamous intraepithelial lesion (SIL) (ASC-L), undetermined significance (ASC-US), and ASC-H. Since the implementation of TBS 2001, we have been reporting ASC as ASC-US and ASC-H. After TBS 2001, our ASC rate decreased from 6.2% to 4% (P < 0.0001). Before TBS 2001, ASC-R carried the same risk as ASC-US for underlying condyloma/CIN 1. Moreover, ASC-R was rarely associated with CIN 2 or 3. Before TBS 2001, ASC-H captured more low-grade (condyloma/CIN 1) and less high-grade (CIN 2, 3, and SCC) lesions compared to after TBS 2001. More women with ASC-H after TBS 2001 underwent colposcopy (80% vs. 71%, P < 0.05). Twenty-two percent of women with ASC-H required 2-4 colposcopies to identify the high-grade lesion. Our results confirm that consistent application of TBS 2001 terminology for ASC reduces the ASC rate, and better identifies women at high risk for CIN 2, 3, and SCC. In addition, ASC-H requires very close clinical follow-up as a significant percentage of women require more than one colposcopy to identify the high-grade lesion.

Cytomorphology of benign breast disease.

Fine needle aspiration biopsy is a widely used technique for the initial diagnosis of mammary lesions. The majority of patients undergoing fine needle aspiration biopsy of a breast lesion will have a benign disease of the breast. This article provides a review of the cytomorphologic features in a variety of benign breast lesions,and discusses the commonly encountered differential diagnoses on aspiration biopsy. Topics discussed include inflammatory and reactive conditions, treatment-induced changes, pregnancy-related changes, benign proliferative lesions, and benign neoplasms of the breast.