Digital image-assisted quantitative nuclear analysis improves diagnostic accuracy of thyroid fine-needle aspiration cytology.

BACKGROUND: Thyroid fine-needle aspiration (FNA) plays a key role in triaging thyroid nodules. Yet many cases are assigned to indeterminate categories. The new category "noninvasive follicular thyroid neoplasm with papillary-like features" (NIFTP) complicates thyroid cytology. Digital image-derived nuclear measurements might objectively distinguish papillary thyroid carcinoma (PTC) from benign nodules and NIFTP. METHODS: All thyroid FNAs from 2012 to 2016 of atypia of undetermined significance (A; n = 8) and suspicious for malignancy (S; n = 2) with sufficient cellularity and surgical follow-up, all FNAs preceding NIFTP (n = 6), and a random sample of PTC (n = 9) and benign (n = 10) cytology were studied. A modified Giemsa-stained slide from each case was scanned using the Aperio imaging system, and long (dl ) and short (ds )-axis diameters were measured for 125 nuclei per case. Nuclear area and elongation were calculated. RESULTS: Nuclear area was larger in PTC (mean, 77.2 µm2 [range, 70.6-86.0 µm2 ]) than benign (mean, 43.3 µm2 [range 38.2-52.2 µm2 ]) (P < .001). Nuclear areas from indeterminate FNAs segregated according to final histology (A/S PTC mean 72.7 µm2 , A/S benign mean 53.7 µm2 ; P = 0.004), and were not significantly different from definitive FNAs of the same diagnosis. NIFTP nuclear area was smaller than PTC (mean, 54.8 µm2 [range, 46.7-66.1 µm2 ]; P < .001). Nuclear elongation showed similar results, but with greater group overlap. CONCLUSION: Nuclear area and elongation can be calculated using a commercial digital imager; both correlate with the final surgical pathology diagnosis of PTC versus benign, including NIFTP. Area provides greater resolution than elongation. This technique could be used to resolve indeterminate cytology in which PTC is considered.

Tissue Acquisition During EBUS-TBNA: Comparison of Cell Blocks Obtained From a 19G Versus 21G Needle.

BACKGROUND: Previous studies have shown that needle gauge size has no significant impact on diagnostic yield during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Our objective was to determine whether cell blocks obtained via the new Flex 19G EBUS-TBNA needle would contain more cellular material based on cell area compared with those obtained from a 21G needle. METHODS: A prospective analysis of patients undergoing EBUS-TBNA at our institutions was performed. Sampling of the same lesion(s) with both the Flex 19G and 21G needles was performed in an alternating manner. In total, 47 patients with suspected lung cancer or mediastinal/hilar lymphadenopathy were included with a total of 83 lesions biopsied. Cell block area was calculated using the Aperio ImageScope software. RESULTS: Mean cell area in the Flex 19G group was 7.34±12.46 mm compared with 5.23±10.73 mm in the 21G group (P=0.02). In the malignant subgroup, the average cell area was 16.16±16.30 mm in the Flex 19G group versus 11.09±15.55 mm in the 21G group (P=0.02). No significant difference was noted in the mean cell area within the nonmalignant subgroup, 1.80±3.01 mm in the 19G group versus 1.56±1.79 mm in the 21G group (P=0.60). CONCLUSION: The cell area obtained via the 19G needle was significantly larger than that obtained with the 21G needle. Further multicenter randomized studies are needed to identify the utility of the Flex 19G needle in diagnosing/subtyping lymphoproliferative disorders and adequacy for molecular testing in non-small cell lung cancer.

Neuroendocrine cell proliferations in lungs explanted for fibrotic interstitial lung disease and emphysema.

Using recently proposed pathological criteria, we determined the incidence of neuroendocrine cell proliferation in a series of explants with lung disease. Cases were defined as NECH (≥3 bronchioles with ≥5 endocrine cells), borderline diffuse neuroendocrine cell hyperplasia (DPNECH) (1-3 tumourlets with or without NECH), and DPNECH (≥3 tumourlets with NECH). Endocrine cells were identified by immunohistochemical staining for synaptophysin. There were 65 explants with interstitial lung disease (57 with non-sarcoid fibrotic lung disease, 8 with sarcoidosis), and 21 with centrilobular emphysema. Over one-third of all explant cases demonstrated histological criteria for NECH. There were three cases of DPNECH in the non-sarcoid fibrotic lung disease group (5%) and 20 cases of NECH (35%). The emphysema group had one case of DPNECH (5%), two cases of borderline DPNECH (10%), and seven cases with NECH (33%). The sarcoidosis group had two cases of DPNECH (25%) and three cases of NECH (38%). NECH is common in interstitial lung disease and emphysema. These results suggest that fibrotic lung disease is a predisposing factor for neuroendocrine cell proliferation, in addition to the known risk of epithelial neoplasms.

Mice with Inflammatory Bowel Disease are Susceptible to Clostridium difficile Infection With Severe Disease Outcomes.

Background: Over the past several decades, there has been a significant increase in the incidence of Clostridium difficile infection (CDI) in patients suffering from inflammatory bowel disease (IBD). However, a wild-type animal model is not available to study these comorbid diseases. Methods: We evaluated the susceptibility to CDI of mice with dextran sulfate sodium salt (DSS)-induced colitis (IBD mice) with or without antibiotic exposure; we examined the histopathology and cytokine response in the concomitant diseases after the model was created. Results: No CDI occurs in healthy control mice, wherease the incidence of CDI in IBD mice is 40%; however, in IBD mice that received antibiotics, the incidence of CDI is 100% and the disease is accompanied by high levels of toxins in the mouse feces and sera. Compared to IBD and CDI alone, those IBD mice infected with C. difficile have more severe symptoms, toxemia, histopathological damage, and higher mortality. Moreover, several proinflammatory cytokines and chemokines are significantly elevated in the colon tissues from IBD mice infected with C. difficile. Conclusions: We, for the first time, demonstrate in an animal model that mice with dextran sulfate sodium induced-inflammatory bowel disease are significantly more susceptible to C. difficile infection, and that the bacterial infection led to more severe disease and death. These findings are consistent with clinical observations, thus, the animal model will permit us to study the pathogenesis of these concurrent diseases and to develop therapeutic strategies against the comorbidity of IBD and CDI.

Biliary stent-related alterations can be distinguished from adenocarcinoma on bile duct brushings using a limited number of cytologic features.

INTRODUCTION: Although it is widely accepted that cytologic alterations secondary to a biliary stent can be difficult to distinguish from adenocarcinoma in pancreatobiliary exfoliative cytology, no systematic study has been undertaken to identify the cytologic features that best distinguish these entities. MATERIALS AND METHODS: A training set of 29 bile duct brushings (14 with biliary stents, originally classified as atypical or suspicious, with >6 months of benign clinical follow-up; and 15 diagnosed as adenocarcinoma with histologic confirmation) was evaluated for the following: nuclear enlargement, nuclear contour, nuclear overlap, chromatin distribution, nuclear-cytoplasmic ratio, anisonucleosis, macronucleoli, mitoses, acute inflammation, disorganization, necrosis, cell borders, single atypical cells, and 2 distinct cell populations. A distinct validation set of 31 equivocal stented brushings-13 later diagnosed with carcinoma and 18 with ≥6 months of benign follow-up-were similarly evaluated. Cases were categorized as benign or malignant using a scoring algorithm based on statistically significant features. RESULTS: Five features achieved statistical significance: atypical single cells (P = 0.0001), 2 distinct cell populations (P = 0.0007), and anisonucleosis (P = 0.0422) favored malignancy; distinct cell borders (P = 0.0018) and acute inflammation (P = 0.0035) favored benign. The algorithm correctly classified 12 of 14 benign and 15 of 15 malignant cases in the training set and 16 of 18 benign and 7 of 13 malignant cases in the validation set. CONCLUSIONS: Most bile duct brushings from patients with biliary stents could be definitively and correctly classified as either benign or malignant using 5 morphologic features: single atypical cells, binary cell population, anisonucleosis, distinct cell borders, and acute inflammation.

Undifferentiated sarcoma of the liver: a case study of an erythropoietin-secreting tumor.

Undifferentiated embryonal sarcoma of the liver (UESL) is an uncommon hepatic tumor usually found in children, with rare cases reported in adults. We present a case of a 53-year-old woman with an undifferentiated sarcoma of the liver (USL), which resembles UESL, who initially presented with a markedly elevated hematocrit (61.2%). Cytogenetic studies for polycythemia vera were negative, but the patient's erythropoietin (EPO) was elevated. A computed tomography scan and subsequent partial hepatectomy revealed a well-circumscribed, partially cystic mass in the right lobe of the liver measuring 34 cm. Following surgery, the patient's EPO level and hematocrit dropped to within normal range and remained so for 1 year, at which point it rose again. A subsequent magnetic resonance imaging scan showed a liver mass at the previous resection margin, consistent with a recurrence. In this case study, we describe the first reported USL resembling an UESL that secretes EPO, which was a useful marker of tumor recurrence.

Pearls and oy-sters: the utility of cytology and flow cytometry in the diagnosis of leptomeningeal leukemia.

Diagnosis of leptomeningeal leukemia (and more broadly, leptomeningeal metastasis [LM]) is based on:

Adenomatoid tumor of the testis with intratesticular growth: a case report and review of the literature.

Adenomatoid tumor of the male genitourinary tract is a rare benign neoplasm thought to be of mesothelial origin. In exceptional cases, these lesions may involve the testicular parenchyma, of which there are only 9 published cases in the literature. The authors describe a rare case of a testicular tumor in a 41-year-old male with normal tumor markers. Histopathology and immunohistochemical studies revealed an adenomatoid tumor with intratesticular growth. No involvement of the epididymis or testicular membranes was identified. The morphological clues leading to the correct diagnosis of adenomatoid tumor and the possible histogenesis and differential diagnosis are discussed.

Cutaneous ciliated cyst: a case report with focus on mullerian heterotopia and comparison with eccrine sweat glands.

Cutaneous ciliated cyst is an exceedingly rare, benign lesion most commonly found in the dermis or subcutis of the lower extremities of young female patients in their second and third decades. The pathogenesis of the cyst is unknown. We report a cutaneous ciliated cyst in the lower extremity of a 13-year-old female patient. On histologic examination, clusters of eccrine sweat glands were observed adjacent to the cyst. Upon comparison of the immunohistochemical profile of the cutaneous ciliated cyst and the eccrine sweat glands, they appeared almost completely unrelated. The histologic, immunohistochemical, and ultrastructural findings of this case and the literature provide evidence in favor of the Mullerian heterotopia theory.

Widespread distribution of reticulon-3 in various neurodegenerative diseases.

Reticulons are a group of membrane-bound proteins involved in diverse cellular functions, and are suggested to act as inhibitors of ß-secretase enzyme 1 (BACE1) activity that cleaves amyloid precursor protein. Reticulons are known to accumulate in the dystrophic neurites of Alzheimer's disease (AD), and studies have suggested that alterations in reticulons, such as increased aggregation, impair BACE1 binding, increasing amyloid-ß production, and facilitating reticulon deposition in dystrophic neurites. To further characterize the cellular distribution of reticulon, we examined reticulon-3 expression in cases of AD, Parkinson's disease, and diffuse Lewy body disease. A more widespread cellular distribution of reticulon-3 was noted than in previous reports, including deposits in dystrophic neurites, neuropil threads, granulovacuolar degeneration, glial cells, morphologically normal neurons in both hippocampal pyramidal cell layer and cerebral neocortex, and specifically neurofibrillary tangles and Lewy bodies. These results are compatible with reticulon alterations as nonspecific downstream stress responses, consistent with its expression during periods of endoplasmic reticulum stress. This emphasizes the increasing recognition that much of the AD pathological spectrum represents a response to the disease rather than cause, and emphasizes the importance of examining upstream processes, such as oxidative stress, that have functional effects prior to the onset of structural alterations.