Rectovaginal endometriosis with nodular smooth muscle metaplasia diagnosed via transrectal ultrasound-guided fine-needle aspiration cytology: An underused minimally invasive diagnostic technique?

Rectovaginal endometriosis is a severe variant of deeply infiltrating endometriosis. Laparoscopic assessment with tissue sampling remains the gold standard for diagnosis of endometriosis. However, transvaginal (TVUS) and transrectal ultrasound (TRUS) have been shown to be especially helpful in the diagnosis of deep endometriosis. We present the case of a 49-year-old female with menorrhagia, dysmenorrhea, and constipation. Upon pelvic examination, an incidental mass was palpated. A computed tomography (CT) scan revealed an anterior rectal wall mass and colonoscopy was non-diagnostic. Further work-up with MRI showed a 3.9 cm mass centered within the upper rectovaginal septum. TRUS guided fine-needle aspiration (TRUS-FNA) revealed cohesive epithelial cell groups without significant cytologic atypia and a second population of bland spindle cells. Cell block slides showed glandular epithelium with associated stroma that exhibited endometrial morphology and immunophenotype. Nodular fragments of spindle cells with smooth muscle immunophenotype and fibrosis were also present. The overall morphologic findings were consistent with rectovaginal endometriosis with nodular smooth muscle metaplasia. Medical management with nonsteroidal aromatase inhibitor with radiologic follow-up was selected. Rectovaginal endometriosis represents a type of deep endometriosis usually associated with severe pelvic symptoms. Metaplastic smooth muscle cells are a frequent component of endometriosis in the rectovaginal pouch with nodular growth and may present diagnostic challenges. TRUS-FNA is a minimally invasive procedure that can provide an accurate diagnosis of endometriosis, even in this variant of deep infiltrating disease.

Oncocytic nodular hyperplasia of the thyroid.

Nodular hyperplasia of the thyroid is a process whereby the gland experiences growth by nodular expansion of thyroid parenchyma. We have encountered 45 patients in whom the process was caused by the growth of well-defined and sharply circumscribed but unencapsulated nodules composed of oncocytic thyroid follicular cells. The lesions arose in 39 women and 6 men, aged 25-69 years (mean = 50.3 years). The surrounding thyroid parenchyma showed features of chronic lymphocytic thyroiditis. The nodules varied from microscopic to 5 cm and appeared to compress the surrounding thyroid parenchyma. Most of the lesions lacked a well-defined capsule. In 26 tumors, the nodules displayed a predominantly follicular pattern of growth; in 8 cases there were admixtures of follicular and trabecular patterns with focal solid areas devoid of follicles. Clinical follow-up in 39 patients ranging from 7 to 22 years (median = 16 years) showed no evidence of recurrence, metastasis, or malignant transformation. One patient died of unknown causes 15 years after the diagnosis, and another patient died 4 years after diagnosis from metastatic colonic adenocarcinoma. Oncocytic nodular hyperplasia is a benign process associated with chronic lymphocytic thyroiditis that should be distinguished from benign and malignant oncocytic (Hurthle cell) tumors of the thyroid.

Assessing the value of second opinion pathology review.

BACKGROUND: Second opinion review of pathology cases can identify diagnostic errors that impact patient care. OBJECTIVE: We sought out to determine discrepancy rates and clinical impact of review of pathology cases to reassess our policy of review on all second opinion cases. METHODS: All second opinion pathology cases over 1 year (2018) were retrospectively reviewed for discrepancy, multiple pathologist review and clinicopathologic features via chart and slide review. Cases were categorized as no significant discordance, major discordance without management change and major discordance with management change. RESULTS: Among 4239 second opinion cases, 3.7% (156/4239) had major discordance with no change in management and 1% (42/4239) had major discordance with change in management. Discordance was significantly associated with multiple pathologist review at our institution (P < 0.001). Highest rates of discordance were observed for thyroid fine needle aspiration (15.3%, 26/170), tissue biopsy of bone/soft tissue (9.6%), endocrine (8.8%), genitourinary (6.7%), gynecologic (6.2%), hematopathology (4%), gastrointestinal/liver (3.7%) and thoracic (3%) sites. CONCLUSIONS: Our study showed a 1% major discordance rate with resulting significant change in clinical management, spread across nearly all subspecialties. Thus, we support recommendations for review of relevant outside pathology material for all patients for which review has the potential to illicit management change such as instituting a major medical or surgical therapy.

The Papanicolaou Society of Cytopathology guidelines for respiratory cytology: Reproducibility of categories among observers.

INTRODUCTION: The Papanicolaou Society of Cytopathology (PSC) has developed a set of guidelines for reporting respiratory cytology. While the malignancy risk for each category is known, the interobserver reproducibility of these diagnostic categories has not been well described. METHODS: Fifty-five cytologic specimens obtained by fine needle aspiration from the pulmonary nodules were independently reviewed by four board-certified cytopathologists and assigned to the diagnostic categories described by the PSC guidelines for respiratory specimens. Statistical analysis for diagnostic accuracy was performed for absolute agreement and chance-corrected agreement (kappa). Differences in frequency of distribution of diagnoses between raters were assessed using the Kruskal-Wallis test. RESULTS: No significant differences in distribution of scores by raters were observed. On average, the absolute agreement was 49.5% and the chance-corrected agreement (kappa) was 20%. 34.5% of interrater comparisons were in full agreement, and total lack of agreement between the four categories was found in 3% of cases. Combining the "suspicious for malignancy" category with the "malignant" category did not significantly alter interrater agreement statistics. CONCLUSIONS: The PSC categories showed only fair reproducibility among four cytopathologists. Agreement between raters was at best fair and did not improve significantly when the categories "suspicious for malignancy" and "malignant" were combined. The most common source of disagreement appeared to be between the categories "suspicious" and "malignant."

Postradiation-associated sclerosing mediastinitis diagnosed in fine needle aspiration specimen: A cytological-pathological correlation.

Sclerosing mediastinitis (SM) is an aggressive fibroproliferative process in the mediastinum that may lead to encasement of mediastinal structures within a dense fibrotic mass. This disease may cause significant clinical complications, morbidity, and even mortality. The etiology and pathogenesis of SM is unclear and in more than one third of cases remains idiopathic. Among the known causes of SM, granulomatous infection is the commonest. Association of SM with radiation therapy has been rarely reported. Herein, we are reporting a case of postradiation sclerosing mediastinitis diagnosed in fine needle aspiration (FNA) specimen. To our knowledge, this is the first reported case of postradiation sclerosing mediastinitis with unusual striking intracytoplasmic glycogen accumulation. Having high index of suspicion and awareness of the fact that this entity may be also associated with radiation therapy, will be helpful in avoiding diagnostic pitfalls in FNA specimens and guiding proper clinical management.

Diagnostic yield of cytopathology in evaluating pericardial effusions: Clinicopathologic analysis of 419 specimens.

BACKGROUND: Pericardial effusions can cause considerable morbidity and potentially may lead to mortality. Malignant pericardial effusions are uncommon, and data on malignancies encountered in pericardial effusion cytology specimens are limited. METHODS: Relevant records of all pericardial effusions from January 2008 to September 2014 were examined and compared with pericardial biopsy results when performed. Discrepant cases were reviewed to determine the cause of the disagreement. RESULTS: In total, 419 pericardial effusion specimens obtained from 364 patients were examined. Cytologic diagnostic categories included: negative for malignancy (332 specimens; 79%), equivocal (25 specimens; 6%), and positive (62 specimens from 51 patients; 15%). Forty-seven patients who had positive effusions were known to have malignancy. The most common primary malignancies were breast (39.3%) and lung (39.3%) cancers in women and lung cancer (47.4%) in men. A concurrent pericardial biopsy was performed in 46% of patients. Excluding equivocal cytologic diagnoses, cytology and biopsy were concordant in 153 of 173 paired samples (88.4%). The sensitivity of cytology in diagnosing malignancy was 92.1% compared with 55.3% for pericardial biopsy. CONCLUSIONS: Cytologic examination has significant diagnostic utility in the evaluation of pericardial effusions and exhibits a lower false-negative rate compared with pericardial biopsy. Submission of pericardial biopsy alongside effusion cytology is associated with increased sensitivity for detecting malignancy and may be especially useful in the setting of low-volume pericardial effusion. Cancer Cytopathol 2017;125:128-137. © 2016 American Cancer Society.

Intratumoral lymphatic vessel density as a predictor of progression-free and overall survival in locally advanced laryngeal/hypopharyngeal cancer.

BACKGROUND: Lymphatic vessel density (LVD) has been shown to be an important predictor of survival in head and neck cancers. We report the predictive value of LVD for progression-free survival (PFS) and overall survival (OS) in laryngeal/hypopharyngeal cancer. METHODS: Fifty-five untreated patients with T3/T4 laryngeal and T4 hypopharyngeal cancer underwent laryngectomy between 1999 and 2010. Surgical specimens were immunostained with D2-40, a specific lymphatic marker. LVDs were determined in tumor vessel "hot spots." Recursive partitioning analysis identified LVD thresholds for both peritumoral (LVDpt) and intratumoral (LVDit) vessels for association with PFS and OS. RESULTS: Patients with mean LVDit of <11 vessels/mm(2) had 2-year PFS and OS rates of 58% and 65%, respectively, compared to 13% and 13% for those with LVDit ≥11 vessels/mm(2) (p = .06 and .04, respectively). CONCLUSION: Intratumoral lymphatic vessel density is predictive of PFS and OS in locally advanced laryngeal/hypopharyngeal cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E417-E420, 2016.

Etiologic factors related to unsatisfactory ThinPrep(®) cervical cytology: Evaluation and potential solutions to improve.

BACKGROUND: In cervical cytology, the unsatisfactory rates for ThinPrep (TP) are slightly higher compared to SurePath. We examined various causes and explored potential for resolution of this discrepancy. MATERIALS AND METHODS: Totally, 19,422 cases were reviewed and 1000 unsatisfactory specimens were selected and analyzed. 531 specimens were available for wash protocol. Out of 114 unsatisfactory specimens associated with atrophic cellular changes (ACC), 48 were resubmitted by provider and reevaluated. RESULTS: Lubricant and lubricant-like debris/contamination (LUBE) was the most common cause of unsatisfactory specimens (68%; 681/1000) followed by blood (7.5%); ACC only (without other interfering factors) (2.4%); inflammation (3.0%); and combinations thereof (1.9%). 11.5% showed scant cellularity without an identifiable cause. 3.3% were virtually acellular. Wash protocol improved cellularity in 48% (256/531) of cases. However, only 29% (73/256) of those were satisfactory (with more than 5000 cells). Quantitative reduction in LUBE after wash protocol varied with different morphological subtypes. Interpretation patterns on satisfactory specimens after wash protocol were comparable to the results on selected cohort of specimens during the same study period. Out of 114 ACC, wash protocol was performed on 68 ACC specimens leading to satisfactory TP in 24% (16/68). Totally, 48 cases reported as unsatisfactory with ACC, were resubmitted by the providers between 2 weeks and 2 years. 44 (92%) showed increased cellularity, out of which 52% (23/44) did not show ACC. CONCLUSION: LUBE was the most common cause of unsatisfactory TP in addition to interference by blood and association with atrophic changes. Knowing the morphological spectrum of LUBE would help to identify it as the cause of unsatisfactory TP. Communicating the cause of unsatisfactory TP such as LUBE, ACC, and blood would hint the provider to take appropriate precaution during submission of the repeat specimen, leading to improved patient care.

Differential Expression of MicroRNAs in Papillary Thyroid Carcinoma and Their Role in Racial Disparity.

OBJECTIVE: MicroRNAs (miRNAs) are known to play important roles in the diagnosis and prognosis of papillary thyroid cancer (PTC), and they are useful in developing targeted therapies. However, there have been no studies on the existence of racial differences in miRNAs expression that could explain differential overall survival of PTC patients. Expression analysis of miRNAs in major racial groups would be important for optimizing personalized treatment strategies. In the current study, we assessed the differential expression of 8 miRNAs between normal and tumor tissues, and also assessed racial differences between African American (AA) and Caucasian American (CA). METHODS: First, the miRNA expression profiling was performed using formalin-fixed paraffin embedded (FFPE) tissue sections of tumor containing over 70% tumor cells. Normal and tumor sections of thyroid tissues were studied from AA and CA patients. The miRNA microarray profiling was done using miRBase version 18 (LC Sciences, Houston, TX, USA). Quantitative real-time PCR (qRT-PCR) was used to validate expression of 8 selected miRNAs. RESULTS: Ingenuity pathway analysis showed involvement of target genes, such as Ras and NF-κB. Deregulated miRNAs such as miR-221 and miR-31 were found to be statistically significant between the two races. Using qRT-PCR, we found that miR-21, miR-146b, miR-221, miR-222, miR-31, and miR-3613 were up-regulated while miR-138 and miR-98 were down-regulated in tumors compared to normal tissues. CONCLUSION: Though sample size was small, we found several deregulated miRNAs having racial differences. The differential expression of miRNAs suggest that these miRNAs and their target genes could be useful to gain further mechanistic insight of PTC and their clinical implications, including miRNA replacement therapy or their knockdown strategies.

Riedel thyroiditis: Fine needle aspiration findings of a rare entity.

Riedel thyroiditis is a rare fibrosing disorder characterized by extension of the fibroinflammatory process beyond the thyroid capsule. Due to the nature of this lesion, fine-needle aspiration often yields scant material and may be interpreted as non-diagnostic. In this report, we describe cytologic features that allow the cytopathologist to favor a diagnosis of Riedel thyroiditis, thereby guiding appropriate further work-up and management.

Cytologic diagnosis of adrenal oncocytic pheochromocytoma in a lung cancer patient: Report of a case and review of the literature.

Adrenal oncocytic pheochromocytoma is an extremely rare type of pheochromocytoma. To the best of our knowledge, we present the first cytological diagnosis of this variant via fine-needle aspiration in an 81-year-old male patient who was found to have an adrenal mass while undergoing workup of the recently diagnosed lung adenocarcinoma. We describe the cytomorphologic findings in our case and provide a review of the reported cases of adrenal oncocytic pheochromocytoma - all of which appear to be benign, nonfunctional, occur in adults, and have similar morphologic features. The pathologist should be aware of this uncommon diagnostic entity and its potential diagnostic pitfalls.

Fine-needle aspiration cytology of the solid variant of papillary thyroid carcinoma: a study of 13 cases with clinical, histologic, and ultrasound correlations.

BACKGROUND: The solid variant of papillary thyroid carcinoma (SVPTC) comprises approximately 3% of thyroid cancers, and there are conflicting reports about its behavior in the literature. The cytology of SVPTC is limited to 3 single case reports, a review article, and a monograph. We present the first cytologic study of SVPTC. METHODS: Fine-needle aspiration smears obtained with ultrasound guidance from 13 patients with histologically pure SVPTC were reviewed, and the cytologic features recorded. Ultrasound images were retrieved from radiology and were correlated with low-power histology images. Intratumor vascularity on Doppler imaging was correlated with cellularity in cytology samples. RESULTS: Three cytomorphologic patterns of SVPTC were identified: cohesive, syncytial-type tissue fragments; microfollicles/trabeculae; and dyshesive single cells. All 3 SVPTCs in the first group were encapsulated without invasion. Two of 6 SVPTCs in the second group had a single lymph node metastasis; 4 were encapsulated, and 2 had pushing borders. Ultrasound images in the first and second SVPTC groups were similar, with the majority revealing a well defined, solid nodule with minimal intranodular vascularity. All 4 SVPTCs in the third group had infiltrative borders; and, with the exception of one 0.8-cm tumor, all had multiple lymph node metastases. Ultrasound in the third group revealed irregular borders. RET/PTC1 and RET/PTC3 mutations were found in 2 cases of the third group. CONCLUSIONS: SVPTCs are heterogeneous tumors. The cohesive, syncytial tissue-fragment pattern can be recognized as SVPTC in smears and is associated with encapsulation and indolent behavior. The microfollicular/trabecular pattern is indistinguishable from that of the follicular variant of papillary thyroid carcinoma and has intermediate behavior. The dyshesive single-cell pattern correlates with infiltrative tumor growth and may not be unique to SVPTC.

Langerhans Cell Histiocytosis: Diagnosis on Thyroid Aspirate and Review of the Literature.

Thyroid gland involvement by Langerhans cell histiocytosis is extremely rare. A 35-year-old woman with a history of a suprasellar mass previously diagnosed as a ganglioglioma and complicated by diabetes insipidus, hypogonadotropic hypogonadism, and central hypothyroidism presented with acute onset of neck enlargement. On ultrasound examination, almost the entire thyroid appeared replaced by abnormal lobulated hypoechoic tissue with increased vascularity. Fine needle aspiration (FNA) of the thyroid was performed and revealed singly scattered and loosely cohesive large cells with abundant cytoplasm, including some with irregular nuclear contours and nuclear grooves. No thyroid follicular cells were noted. Based on the cytomorphologic findings and ancillary studies (immunohistochemistry and flow cytometry analysis) a cytological diagnosis of "positive for neoplastic cells" with features suggestive of monocytic/histiocytic origin, possibly Langerhans cell histiocytosis (LCH) was rendered. Following FNA, the patient underwent an incisional thyroid biopsy that confirmed the cytological impression of LCH. In light of the new diagnosis of LCH, the prior suprasellar mass biopsy slides were re-reviewed and rare cells suspicious for LCH were observed. Appropriate treatment for systemic LCH was initiated successfully. This case demonstrates that the presence of enlarged and loosely cohesive cells, especially those with irregular nuclear contours, in thyroid FNA specimens should raise suspicion for LCH. The diagnosis of LCH in FNA specimens is challenging. Additional material should be allocated for ancillary studies to confirm the morphological impression. In our case, not only was the thyroid FNA crucial in diagnosing LCH, but instrumental in initiating a thorough diagnostic work-up for multisystem involvement and thus unmasking the true etiology of the patient's suprasellar mass and associated endocrinopathies.

Fine-needle aspiration diagnosis of high grade adenoid cystic carcinoma metastatic to the pancreas.

Pancreatic tumors are mostly primary tumors, with only rare metastatic tumors described in the literature. Here we report an unusual case of fine-needle aspiration (FNA) diagnosis of high grade adenoid cystic carcinoma of the parotid gland metastatic to the pancreas. The aspirate smears were moderately cellular and revealed numerous basaloid neoplastic cells. The cytomorphologic differential diagnosis included primary pancreatic tumor with small cell morphology as well as metastatic tumors. By immunocytochemistry, the tumor cells were positive for cytokeratins (AE1/AE3, CAM5.2, and CK7), and CD117 (C-KIT), and negative for CD45, WT1, synaptophysin, chromogranin, CD56, TTF-1, and CK20. The cytomorphologic features and immunoprofile in our case were consistent with high-grade carcinoma metastases from patient's known salivary gland primary. To the best of our knowledge, this case is the first reported encounter of FNA diagnosis of pancreatic metastasis with small cell morphology from a salivary gland neoplasm as primary site.

Demonstration of the role of an implantable bioscaffold in airway reconstruction: a pilot study utilizing an animal model.

INTRODUCTION: Laryngotracheal reconstruction is a common procedure to repair subglottic stenosis. Despite a success rate upwards of 85%, this procedure has significant morbidity associated with it, specifically with the site of the graft harvest and recurrence of stenosis. We propose that a recently described cellular bioscaffold xenograft may be useful in reducing these complications. METHODS AND MATERIALS: 10 Sprague Dawley rats were divided into 2 groups of 5. One group underwent incision through the cricoid and the first two tracheal rings followed by primary closure (G1); the second group underwent incision through the cricoid and the first two tracheal rings followed by placement of the xenograft (G2); additionally, a specimen was harvested from an animal which did not undergo any surgical procedure to compare to the two surgical groups. Specimen harvest occurred on post-operative days 1, 7, 14, 21, and 28. RESULTS: 6 of 10 animals provided usable data. All animals receiving the xenograft survived until the time of specimen harvest. Only 1 animal undergoing primary closure survived beyond post-operative day one. On histology review, the xenograft animals showed a progressive decrease in fibrosis relative to the animals that underwent primary closure. On POD 28, restoration of the respiratory epithelium and intact basement membrane was noted in the xenograft group. CONCLUSION: We believe that this pilot study shows the potential of utilizing bio-implantable biomaterials, specifically a cellular bioscaffold which encourages the ingrowth of native tissue instead of fibrosis. Histologic analysis shows that use of the xenograft can initiate the proliferation of native tissues decreasing the amount of fibrosis present post-operatively, although significant further analysis is needed before definitively concluding that this approach is superior to utilization of a graft.

Metastatic colorectal adenocarcinoma in cervicovaginal cytology specimens confirmed by immunocytochemical stains on liquid base specimens: Two study cases with review of the literature.

Only a few cases of adenocarcinoma (ACA) metastatic to the female lower genital tract diagnosed on cervicovaginal Pap smear have been reported during the past several decades. Both conventional and liquid based cytology (LBC) have limited sensitivity and specificity in diagnosing metastatic disease and immunocytochemical (ICC) staining may be needed for confirming the diagnosis. We present two cases of metastatic colorectal ACA diagnosed on cervicovaginal ThinPrep (TP) Pap smears, with one confirmed by ICC staining method. Recognition of extra-uterine malignancy in the cervicovaginal cytology specimen is critical for the disease diagnosis, prognosis, and the treatment. ICC staining performed on the residual LBC specimen is an important methodology to confirm the diagnosis.

Fine needle aspiration cytology of primary sphenoid sinus esthesioneuroblastoma metastatic to the skin.

Esthesioneuroblastoma (ENB) is a rare tumor derived from olfactory neuroepithelium. ENB in a site outside of where olfactory epithelium exists is exceedingly rare with only five cases of ENB isolated to the sphenoid sinuses described in the literature to date. To the best of our knowledge, a skin metastasis of ENB outside the head and neck region has not been reported. We present an unusual case of a 33-year-old male diagnosed with primary sphenoid sinus ENB, who underwent surgical resection of the tumor followed by chemoradiation. About 5 months later, the patient developed a dermal mass in the sternal region, clinically suspicious for metastasis. Fine needle aspiration (FNA) revealed a tumor with morphological features and immunophenotype consistent with the metastasis from patient's known primary sphenoid sinus ENB. Our case demonstrates that the skin may be a rare site of a metastatic ENB, and FNA is a cost-effective and reliable diagnostic method of a suspected cutaneous metastasis.