A Case of Distal Common Bile Duct Obstruction Due to a Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) are a rare subset of malignancies in the biliary tract that may have an aggressive and initially asymptomatic course. A 93-year-old female presented with four days of abdominal pain with associated nausea, jaundice, and brown-colored urine. A CT scan revealed a soft-tissue lesion measuring 1.9 x 1.5 x 1.9 cm within the distal-most aspect of the common bile duct and papilla with marked bile duct dilatation, pancreatic duct dilatation, and multiple hepatic lesions of varying sizes. The biliary stricture was palliated with a stent via endoscopic retrograde cholangiopancreatography. Biopsies taken from the biliary mass were consistent with a well-differentiated NET: World Health Organization, Grade 3. The patient was minimally symptomatic after stenting and was discharged home. She ultimately decided not to pursue further treatment and passed away two months after the initial presentation. Currently, surgical excision is considered the main and only curative treatment for localized NETs, although chemotherapy and radiation therapy may be suitable. Early detection and treatment of these rare NETs in the biliary tree can potentially result in curative treatment.

Oncocytic Follicular Cell-Derived Thyroid Tumors With Papillary Growth Pattern: A Clinicopathologic Study of 32 Cases.

CONTEXT.­: Oncocytic thyroid tumors displaying a papillary growth pattern are rare and may cause diagnostic problems. OBJECTIVE.­: To examine the clinicopathologic features of a series of 32 follicular cell-derived tumors composed of cells with oncocytic cytoplasm and displaying papillary architecture. DESIGN.­: Thirty-two cases were collected and studied to assess clinicopathologic features, including immunohistochemical and molecular testing for BRAF V600E. RESULTS.­: The patients were 26 women and 6 men, aged 17 to 77 years. The nodules ranged from 0.3 to 6.0 cm. Eighteen cases showed features of oncocytic hyperplastic nodules and were identified against a background of thyroid follicular nodular disease; 4 cases showed features of oncocytic follicular adenoma; and 10 cases corresponded to carcinomas with oncocytic and papillary features. Nuclear features of papillary thyroid carcinoma were absent or exceedingly rare. All cases were negative for HBME-1 and cytokeratin 19 (CK19) and wild type for BRAF V600E. Follow-up in 25 patients showed that all patients with hyperplastic nodules and oncocytic follicular adenomas were alive and well and free of disease from 7 to 20 years. One patient with oncocytic follicular carcinoma showed metastases and died of tumor at 16 months; 2 patients with carcinoma had metastases and recurrence at 6 and 7 years; and 5 patients with invasive tumors were free of disease from 5 to 10 years. CONCLUSIONS.­: Oncocytic thyroid tumors with papillary features can span a spectrum from benign hyperplastic, to encapsulated neoplastic, to invasive malignant lesions. Owing to their papillary features, it is important not to confuse them for other types of thyroid tumors, such as oncocytic papillary thyroid carcinoma.

Comprehensive Review of Anal Cytology.

BACKGROUND: The incidence of anal cancer has increased over at least the past decade, with estimates of a continued increase in the coming years. Women are more commonly affected than men in the general population; separate high-risk populations have also been identified. While the pathophysiology of anal cancer is thought to be similar to its cervical counterpart, well-defined and standardized screening guidelines have not been established as is seen in cervical cancer prevention. Nonetheless, multiple screening modalities have been examined and are components of proposed institutional and societal screening programs. SUMMARY: Anal cytology is one modality that is a mainstay of many suggested screening guidelines. Interpretation and reporting follow current criteria for cervical/vaginal cytology per the Bethesda System, with site-specific alterations and changes in adequacy criteria to better accommodate some of the confounding factors encountered in anal cytology. While there are some limitations, such as a tendency to underestimate the degree of dysplasia and variable interobserver concordance rates, anal cytology, especially liquid-based preparations, overall performs well in detecting anal abnormalities and acts as an adequate screening tool. Importantly, most anal squamous dysplasias and cancers are also associated with human papillomavirus (HPV) infection, raising the possibility of HPV testing or genotyping as a component of screening and/or follow-up. Studies have also shown the efficacy of HPV vaccination in preventing anal lesions. Digital anorectal exam as well as anoscopy, particularly high-resolution anoscopy, are also often components of screening and follow-up. Management guidelines such as those put forth by the American Society for Colposcopy and Cervical Pathology (ASCCP) for cervical cancer are also not established for anal cancer. However, studies such as the Anal Cancer HSIL Outcomes Research (ANCHOR) trial have made significant strides in demonstrating successes in follow-up and treatment of anal lesions, findings that are crucial for establishing prevention and management guidelines going forward.

A rare case of sebaceous lymphadenoma: Cytohistological correlation of preoperative cytomorphologic findings.

We are presenting a case of a 74-year-old female with a parotid gland mass. Fine-needle aspiration (FNA) of the mass demonstrated cohesive groups of epithelial cells with overall bland-appearing nuclei and abundant vacuolated cytoplasm, consistent with sebaceous cells, in a background of polymorphous lymphocytes, scattered histiocytes, and adipose tissue. Immunostains showed that the epithelial cells stain positive for p63, but negative for CD117 and DOG-1. CD3 and CD20 showed a mixture of T- and B-cells. On the PAP-stained slides, there were numerous sac-like structures, consistent with myospherules. These findings were suggestive of neoplasm with sebaceous differentiation. The main differential diagnosis included sebaceous adenoma, sebaceous lymphadenoma, and other benign lesions with sebaceous differentiation. The parotid mass was resected. Histology sections demonstrated a well-circumscribed neoplasm with multicystic epithelial component and surrounding lymphoid infiltrate, consistent with sebaceous lymphadenoma. Sebaceous lymphadenoma (SLA) is a rare benign salivary gland neoplasm that is most commonly seen in the parotid gland. Preoperative FNA diagnosis of sebaceous neoplasms is challenging. To the best of our knowledge, this is the third case of sebaceous lymphadenoma diagnosed preoperatively. In this manuscript, we detail the epidemiological characteristics and histogenesis of sebaceous salivary gland neoplasms, and the cytomorphologic differential diagnosis of SLA with key diagnostic features of each entity.

The value of 'raspberry bodies' in intraoperative cytologic evaluation of adnexal masses for the diagnosis of clear cell carcinoma of the ovary: A cytological-pathological correlation.

We report a case of a 48-year-old female who presented to the emergency department with pelvic/abdominal pain and a recent history of irregular periods. Pelvic ultrasound and computed tomography (CT) scan of the abdomen/pelvis revealed a 7.3 cm adnexal mass with suspicious features. During the intraoperative evaluation, a frozen section slide and a cytological smear were prepared. The cytological preparation was moderately cellular, showing cohesive groups of atypical cells with anisonucleosis, high nuclear to cytoplasmic ratio, and oval nuclei with prominent nucleoli. The tumor cells surrounded extracellular, magenta hyaline globules, forming raspberry bodies. Raspberry bodies are comprised of basement membrane deposits and are a unique finding in ovarian clear cell carcinoma. Raspberry bodies were also found in the frozen section slide, but, in comparison to the cytological preparation, were rare, difficult to identify, and resembled necrotic debris. The intraoperative diagnosis of a clear cell carcinoma is important because the surgical management will be more aggressive, as optimal tumor debulking is shown to have better overall survival. In this manuscript, we detail the intraoperative evaluation of an ovarian mass, the utility of cytological preparation and importance of identifying raspberry bodies in the evaluation of ovarian masses, and surgical management of clear cell carcinoma.

Small cell carcinoma of the urinary bladder: Distinctive cytological characteristics and Cyto-histologic correlation.

Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has not been described in detail in the literature. A 79-year old male presented at our institution with gross hematuria. He was accurately diagnosed with small cell carcinoma of the bladder on liquid-based cytology in urine. The patient subsequently proceeded to transurethral resection of the bladder tumor, confirming the diagnosis. In this article, we present a detailed report of primary urothelial carcinoma with dominant neuroendocrine differentiation of the bladder describing the cytologic and histologic morphologic features, its differential diagnosis with a review of the literature.

Primary pulmonary mucoepidermoid carcinoma: Cyto-histologic correlation and review of the literature.

Preoperative fine needle aspiration diagnosis and cyto-histologic correlation of primary pulmonary mucoepidermoid carcinoma have rarely been described in detail in the literature. A 26-year old male presented at our institution with cough, bloody sputum, and a 4.3 cm left lower lobe lung mass. He was accurately diagnosed with pulmonary mucoepidermoid carcinoma on preoperative aspiration cytology. The patient subsequently proceeded to left lower lobectomy, confirming the diagnosis. In this article, we present a detailed report of primary pulmonary mucoepidermoid carcinoma describing the cytologic and histologic morphologic features, its differential diagnosis with review of the literature.

Correlation of anal cytology with follow-up histology and Human Papillomavirus genotyping: A 10-year experience from an academic medical center.

BACKGROUND: Anal cytology (AC) is accepted as a practical screening modality for anal cancer. However, studies suggest that AC and anal biopsy dysplasia correlation is less robust than in cervicovaginal specimens. The current study goals were to look at our institutional experience in a subset of ACs and correlate with surgical pathology (SP), as well as evaluate their Human Papillomavirus (HPV) status. METHODS: 377 ACs from 169 patients (151 males and 18 females) from 2008 to 2017 were included. HPV genotyping (n = 47) and SP within one year of AC (n = 58) were reviewed. RESULTS: AC/SP was discrepant in 22 cases (37.9%), with a tendency towards AC underestimating the degree of dysplasia. Specifically, any abnormality on AC was 93.8% sensitive for detecting high-grade dysplasia (HGD). However, when requiring a high-grade AC diagnosis, the sensitivity decreases to 12.5%. "Other high-risk HPV" was the most common genotype (57.4%). When considered with all AC with a high-grade diagnosis, co-testing with HPV improved the sensitivity for HGD to 56.3%. Sensitivity improved further to 87.5% when only considering cases with both AC and HPV testing, and were high-risk HPV positive. Furthermore, following review and consensus diagnosis, 8 cases changed from "Discrepant" to "Agreed", reducing the discrepancy rate to 24.1%. Remaining discrepancies were explained by sampling error. CONCLUSION: Given the enhanced sensitivity of AC and HPV testing together, and sampling error seen with AC leading to underestimating dysplasia, we recommend AC and HPV co-testing, as well as describing confounding factors in AC reports and obtaining consensus opinion in equivocal cases.

Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity.

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described "squamoid cyst of the pancreatic ducts", the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name "intraductal papillary squamous neoplasm of the pancreas." Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.

Metastatic atypical meningioma to the parotid gland - A cytopathological correlation.

The tumors involving the parotid gland are mainly primary, with metastatic lesions comprising only 5% of malignant salivary gland neoplasms. We are presenting a rare case of metastatic meningioma to the parotid in a 51-year-old male with a past medical history of recurrent atypical meningioma involving the frontal lobe. For the past 1.5 years, routine imaging showed parotid lesions with interval growth including a 2.0 cm dominant tender preauricular parotid mass. The chronicity and the number of lesions made malignancy unlikely. The differential diagnosis included non-specific lesions such as intraparotid lymph nodes and benign neoplasms. Fine needle aspiration of the parotid mass was performed to show loosely cohesive fragments and singly scattered neoplastic cells with mild nuclear pleomorphism and oncocytic cytoplasm. The main cytomorphologic differential diagnosis included oncocytic and myoepithelial-rich tumors. The neoplastic cells were immunoreactive to p63, calponin and SSTR2A and were negative for cytokeratins, progesterone receptor, S100, DOG-1, EMA, synaptophysin, and chromogranin. The cytology slides and the parotid gland mass resection were compared to the previous meningioma resection specimen which showed a similar morphology of the oncocytic tumor cells in some areas. The overall morphologic and immunohistochemical findings of the parotid tumor were consistent with metastatic meningioma. Extracranial metastases from intracranial tumors are extremely rare. Meningiomas arise from the dura matter, constitute 15% of primary brain tumors, and metastasize at an estimated rate of 0.1%. Despite how uncommon metastatic meningioma is, our case emphasizes the critical role of clinical history when evaluating parotid gland lesions.

Cystic Lesions of the Pancreas: Differential Diagnosis and Cytologic-Histologic Correlation.

CONTEXT.­: Pancreatic cystic lesions (PCLs) are very common, and their detection is increasing with the advances in imaging techniques. Because of the major implications for management, distinguishing between neoplastic and nonneoplastic PCLs is critical. Neoplastic cysts with potential to progress into cancer include mucinous PCLs (intraductal papillary mucinous neoplasms and mucinous cystic neoplasms) and nonmucinous cysts (solid pseudopapillary tumors, serous cystic neoplasms, and neuroendocrine tumors with cystic degeneration). Nonneoplastic cysts with no risk of malignant transformation include pseudocysts, retention cysts, lymphoepithelial cysts, cystic pancreatic lymphangioma, and duplication cyst/ciliated foregut cysts. The role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology with cyst fluid analysis in the diagnosis of PCLs has evolved during the last decade; however, a definitive diagnosis on cytologic specimens is hampered by the sparse cellularity and can be challenging. EUS-FNA can play an important role to differentiate low-risk from high-risk pancreatic cysts and to distinguish between patients with cysts who need clinical follow-up versus those who require surgery. OBJECTIVE.­: To provide an integrative approach to diagnose pancreatic cystic lesions using EUS-FNA cytology and cyst fluid analysis, along with clinical, radiologic, histologic, genetic, and molecular characteristics. DATA SOURCES.­: The review and analysis of the latest literature describing pancreatic cystic lesions. CONCLUSIONS.­: Accurate diagnosis of PCLs requires a multidisciplinary and multimodal team approach, including the integration of clinical findings, imaging, cytology, cyst fluid analysis, and molecular testing.

Coexisting pancreatic serous cystadenoma and pancreatic ductal adenocarcinoma: A cytological-pathologic correlation with literature review.

Pancreatic serous cystadenoma (SCA) is a benign neoplastic lesion with a distinctive gross and microscopic appearance consisting of numerous thin-walled cysts lined by uniform epithelial cells with clear cytoplasm and small nuclei. The vast majority of serous cystadenomas are benign. Pancreatic SCA has rarely been reported in association with other pancreatic lesions. We present a challenging case in which a cystic and solid pancreatic mass was identified on imaging studies. FNA was performed and showed clusters of atypical cells with significant nuclear pleomorphism (>4:1), disorganized, overlapping nuclei, and prominent nucleoli. The FNA diagnosis was positive for malignancy, consistent with adenocarcinoma. The patient underwent neoadjuvant therapy and pancreaticoduodenectomy. Final pathology showed a serous cystadenoma associated with small foci of high-grade PanIN. The lack of invasive adenocarcinoma in the resection specimen was most likely due to complete response of the tumor to neoadjuvant chemoradiation therapy, but it is also possible that only high-grade PanIN was present initially. To our knowledge, this is the first reported case of SCA and high grade PanIN/PDAC that was assessed by FNA. We discuss the cytologic differential diagnosis and how to avoid potential pitfalls highlighted by this case.

Cytologic features of pancreatobiliary neoplasm of duodenum.

Small intestinal adenomas are uncommon. Majority of these occur in the region of the ampulla of Vater. Adenomas of the ampulla can be further subdivided into two types-intestinal and pancreatobiliary. While intestinal adenomas are more frequent, pancreatobiliary adenomas are rare. There is limited literature regarding the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) in the diagnosis of ampullary/peri-ampullary neoplasms. Here, we describe the cytologic features of a pancreatobiliary neoplasm of the duodenum that was sampled by EUS-FNA. The aspirate was cellular and revealed cells with moderately abundant oncocytic cytoplasm. The nuclei were round with fine chromatin and focally prominent nucleoli. Although the concurrent biopsy showed no high-grade dysplasia or invasive carcinoma, the EUS and imaging findings were highly suspicious for invasion. A broad differential diagnosis is under consideration for a duodenal mass that encompasses neoplasms of the biliary tract, pancreas, duodenum, and ampulla of Vater. To our knowledge, cytologic features of a pancreatobiliary neoplasm of the duodenum have not been previously reported. Our case highlights the features seen on cytology with histologic correlation in the hopes of elucidating features to better characterize these lesions.

Choroidal melanoma diagnosed by aspiration cytology: A case report with cyto-histologic correlation and review of the literature.

Histologic and cytologic features of uveal melanomas have been well characterized; however, cytologic-histologic correlation has rarely been described in detail in the literature. A 50-year old female presented at our institution with an intraocular mass which was diagnosed as choroidal melanoma by aspiration cytology. The patient subsequently proceeded to enucleation, confirming the diagnosis. Cytology revealed epithelioid cells containing melanin pigment and only mild nuclear atypia. The enucleation specimen contained 90% epithelioid cells with similar cytomorphology and an additional 10% spindle cell component not observed in the aspiration cytology. In summary, we present a case of choroidal melanoma showing high concordance between cytologic and histologic morphologic features.

The Milan system for reporting salivary gland cytopathology: A study of inter-observer reproducibility.

BACKGROUND: In 2018, the Milan System for Reporting Salivary Gland Cytopathology was published defining a diagnostic categorization scheme with known malignancy risks and clinical follow up recommendations. Inter-observer reproducibility of the categories was not defined. METHODS: Salivary gland fine-needle aspirations (FNA) were reviewed over a 5 year period and classified by three independent observers. Inter-observer reproducibility was estimated using observed agreement and chance corrected agreement (Cohen's kappa). RESULTS: Four hundred and eight cases were reviewed with chance corrected agreement of 0.42 for the original Milan System and 0.48 for a modified system using "similar follow up" categories. Categories 4A and 6B showed substantial agreement (kappa =0.71 and 0.72). CONCLUSION: The Milan System shows moderate over all agreement between observers. Strongest inter-observer agreement was seen for categories 4A and 6B.

Sensitivity and specificity of fine needle aspiration for the diagnosis of mediastinal lesions.

Fine needle aspiration cytology (FNAC) of mediastinal masses allows for rapid on-site evaluation and the triaging of material for ancillary studies. However, surgical pathology is often considered to be the gold standard for diagnosis. This study examines the sensitivity and specificity of FNAC compared to a concurrent or subsequent surgical pathology specimen in 77 mediastinal lesions. The overall sensitivity for mediastinal mass FNAC was 78% and the overall specificity was 98%. For individual categories the sensitivity and specificity of FNAC was respectively as follows: inflammatory/infectious (33%, 99%), metastatic carcinoma (93%, 100%), lymphoma (84%, 97%), cysts (25%, 100%), soft tissue tumors (100%, 100%), paraganglioma (50%, 100%), germ cell tumor (100%, 99%), thymoma (87%, 94%), thymic carcinoma (60%, 100%), benign thymus (0%, 100%), and indeterminate (100%, 90%). For different locations within the mediastinum the sensitivity and specificity of FNAC was respectively as follows: anterosuperior mediastinum (80%, 98%), posterior mediastinum (33%, 95%), middle mediastinum (100%, 100%), and mediastinum, NOS (79%, 99%). Thus, mediastinal FNAC is fairly sensitive, very specific, and is a valuable technique in the diagnosis of mediastinal masses.