Irregular Nuclear Membranes Research Articles

A case report and review of oncocytic variant of papillary thyroid carcinoma

Aim To present a case of oncocytic variant of papillary thyroid carcinoma and review the literature on this uncommon variant. Case report A 60-year-old male underwent a total thyroidectomy and right cervical level six lymph node dissection for a suspected papillary thyroid carcinoma based on FNA. The thyroid gland contained two nodules in the right lobe, 10 mm and 23 mm, both with a tan lobulated cut surface. Histologically, the smaller nodule was an adenomatoid nodule and the larger was an oncocytic variant of papillary thyroid carcinoma. The carcinoma cells possessed classic oncocytic morphology, positivity for succinate dehydrogenase complex subunit B (SDHB) and the characteristic nuclear features of papillary thyroid carcinoma – enlarged nuclei with pale chromatin, nuclear membrane grooves and irregularities, and intranuclear pseudoinclusions. Somewhat unusually, the cells were negative for Galectin-3 and HBME-1. There was lymphovascular invasion and three lymph node metastases were found. Discussion The oncocytic variant of papillary thyroid carcinoma can provide a diagnostic challenge, with possible differentials including oncocytic variants of follicular adenoma and carcinoma, medullary thyroid carcinoma and hyalinising trabecular tumour. With varying reports on its immunohistochemical profile, the nuclear features of papillary thyroid carcinoma remain the most useful diagnostic criteria for this tumour.

A Case of Reticulohistiocytoma Mimicking Primary Cutaneous CD 4 Positive Small/medium T-cell Lymphoma

Reticulohistiocytoma is a rare, benign histiocytic proliferation of the skin or soft tissue. A 5-month-old healthy girl visited our clinic for an enlarging nodule on the center of her right palm. The clinical differential diagnosis included xanthogranuloma and primary cutaneous CD4 positive small/medium T-cell lymphoma. Histopathology of the nodule showed abundant eosinophilic and glassy cytoplasm. The nuclei were round to oval shaped, with focal irregular nuclear membrane, and mitotic figures were absent. Immunohistochemical study determined that the cells were positi ve for CD68 but negative for CD1a. She was finally diagnosed with reticulohistiocytoma (solitary epithelioid histiocytoma).

Hematologic lesions in urine cytology

Bladder infiltration by leukemia or lymphoma is rare and can mimic benign processes such as follicular cystitis (FC). Eight benign and malignant hematologic diseases encountered in urine cytology were retrospectively reviewed for clinical, radiographic, and cytologic findings. There were 2 cases of acute myeloid leukemia, 2 cases of diffuse large B-cell lymphoma, and 4 cases of FC. The most common presenting symptom was hematuria. Imaging findings included echogenic debris within the bladder or an adjacent soft tissue mass in acute myeloid leukemia cases and bladder wall thickening in diffuse large B-cell lymphoma cases. No FC cases had any imaging abnormalities. Cytologic material of the leukemia cases showed numerous myeloid blasts with markedly increased nuclear-to-cytoplasmic ratios, centrally located nuclei, inconspicuous nucleoli, nuclear indentations, and some irregular nuclear membranes. The background showed sparse urothelial cells and histiocytes. Both lymphoma cases showed a discohesive population of atypical large lymphoid cells with irregular nuclear borders and prominent nucleoli. The FC cases had a background lymphoid cell population with a maturation spectrum from small lymphocytes to large lymphoid cells (immunoblasts) and histiocytes including tingible body macrophages. Additionally, there were many mature squamous cells and reactive urothelial cells. Bladder leukemia, lymphoma, and FC are infrequently encountered on urine cytology. FC can be distinguished from a hematologic malignancy by the presence of a lymphocytic maturation spectrum and tingible body macrophages. Radiologic abnormalities are associated with malignant processes; however, discrete bladder masses are usually not identified.

EFFECT OF BASIC FIBROBLAST GROWTH FACTOR ON BEHAVIOR ABILITY AND NEURONS OF THE HIPPOCAMPAL CA3 AREA IN ALZHEIMER'S DISEASE MODEL RATS

The study aimed to examine the behavior ability and morphological changes in neuron in the hippocampal CA3 area of Alzheimer's disease (AD) model rats induced by β-amyloid protein (Aβ1–42) and observe the potentiality of the neuroprotective effect of basic fibroblast growth factor (bFGF) on the AD model rats. A total of 70 Wistar rats were randomly divided into the normal control group, the AD model group and the bFGF treatment group. The AD model rats were established by microinjection of Aβ1–42 solution into right hippocampal CA1 area. The bFGF was injected into the abdominal cavity of rats in the bFGF treatment group, and identical volume physiological saline was given for the other two groups. The colorimetric method was used to detect the choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) activity after the behavior capability was determined. Real time-PCR (RT-PCR) was used to evaluate the expression of VEGF mRNA of the rat hippocampal CA3 area. Caspase-3 immunopositive cells in the hippocampal CA3 area were observed under a light microscopy and quantitative analysis were performed by cell morphometric technique. The ultra-microstructure of the neurons was also observed by a transmission electron microscopy (TEM). The results indicated that compared with the AD model group, the learning and memory abilities of the bFGF treatment group were obviously improved and the ChAT activity significantly increased (p < 0.05), whereas the AChE activity, expression of VEGF mRNA and quantity of Caspase-3 immunopositive cells notably decreased (p < 0.05). Under TEM, the neurons in the hippocampal CA3 area of the normal control group had moderate electron density, rule nucleus, integrity perinuclear membrane, evenly distributed chromoplasm and abundant cell organelle, however the neurons of the AD model group showed severely damaged, exhibiting cell body pyknosis, irregular nuclear membranes concentrated, intracytoplasm content concentrated, decreased or unclear organelles. The neuronic pathological lesion of the bFGF treatment group had lessened than that of the AD model group; some of them had distinct neuronal structure and abundant cell organelle. BFGF could efficiently improve the behavior ability and decrease the pathological lesion of hippocampus of the AD model rats, which might promote the neuroprotective effect in the AD.

Intraoperative imprint cytology of ovarian transitional cell (Brenner) tumors: A retrospective study

Literature on fine-needle aspiration of ovarian transitional cell tumor or Brenner tumors is sparse and mostly confined to isolated case reports of metastatic transitional cell tumors. We undertook a retrospective study of intraoperative imprint cytology of ovarian transitional cell tumors to better define the cytologic features of this uncommon ovarian tumor. Between 2005 and 2012, a total of 19 ovarian transitional cell tumors were recorded in our surgical pathology files, 10 of which had concomitant imprint cytologic material available for review. The 10 patients included in this study ranged in age between 43 and 73 years (mean age: 54 years). Nine neoplasms were histologically benign and one was borderline. Nine cases had satisfactory cytologic material for review. The cytologic features can be summarized as follows: the eight benign tumors showed abundant naked nuclei in the background, small and large clusters of tumor cells, abundant cytoplasm, smooth nuclear membranes, and lack of nuclear pleomorphism and mitoses. Single plasmacytoid cells with dense blue abundant cytoplasm, perinuclear vacuoles, nucleoli, microfollicle formation, nuclear grooves, binucleation/multinucleation, and extracellular eosinophilic material were some of the other features that were appreciated. The cytologic features of the one case of borderline transitional cell tumor were similar to those of the benign tumors except for the presence of rare mitoses, easily identifiable nuclear pleomorphism and irregular nuclear membranes. This study highlights some characteristic cytologic features of benign/borderline transitional cell tumors of the ovary which can be of help in recognizing this uncommon neoplasm.

Nuclear morphometric and morphological analysis of exfoliated buccal and tongue dorsum cells in type-1 diabetic patients

Background:Diabetes mellitus type 1 that results from immunologically mediated damage to the β-cells in the pancreas. Diabetes mellitus is characterized by recurrent or persistent hyperglycemia. Hyperglycemia can be associated with salivary gland dysfunction and alterations in the oral epithelial cells.Aim:The aim of this study was to evaluate the qualitative and quantitative changes in buccal and tongue dorsum epithelial cells using an exfoliative cytology method in type 1 diabetic patients.Materials and Methods:We performed light microscopic analysis of the buccal and tongue dorsum smears in thirty type 1 diabetic patients and thirty healthy individuals. The oral smears were stained using Papanicolaou method for cytological examination and nuclear morphometric analysis. In each case, the mean nuclear area, perimeter, length, breadth, and roundness factor were evaluated in each smear using the image analysis software (Q Win, Leica™).Results:The nuclear area, length, breadth, and perimeters were significantly higher in the diabetic group from tongue dorsum smear than that of the control group (P < 0.05). In the cytological examination, karyorrhexis-karyolysis-karyopyknosis, binucleation, nuclear membrane irregularity, cytoplasmic polymorphism, perinuclear halo were observed in oral smears with type 1 diabetic patients. Binucleation (P = 0.002) and nuclear membrane irregularity (P = 0.024) were significantly more common in buccal smears of diabetic group. Furthermore, the sensitivity of buccal mucosa was significantly higher in the diabetic group (P = 0.006).Conclusion:The light microscopic and nuclear morphometric study indicates that type 1 diabetes can produce morphological and nuclear morphometric changes in the oral mucosa that are noticeable with exfoliative cytology.

Use of Vaginal Lubrication Containing Carbomer Affects Adequacy of ThinPrep Pap Test

Introduction: High grade tubo-ovarian serous adenocarcinoma is a significant cause of mortality. In recent years attention has turned to the fallopian tube as a primary source of precursor neoplastic lesions. The cytologic features of fallopian tube brushings from low risk patients have not been well described in modern cytology literature. Material and Methods: We describe the cytomorphologic features of tubal epithelium from prospectively collected experimental in vivo brushings of normal fallopian tubes from low risk patients. Both ThinPrep slides and cell blocks were prepared and reviewed in all specimens. P53 and Ki-67 immunostains were also performed when epithelial cells were detected in cell block specimens. Available follow-up histopathologic salpingectomy material was also reviewed. Results: A total of 15 specimens were obtained from 7 patients, ten collected by laparoscopy, 4 by hysteroscopy, and one after hysterectomy and bilateral salpingo-oophorectomy on an ex-vivo specimen. Cytologic findings were as followscellularity: moderate to high (nZ13), low (nZ2); background: granular debris (nZ10), clean (nZ4), blood (nZ1); architecture: mixture of clusters and single cells (nZ11), clusters (nZ3); nuclear overlap: moderate/marked (nZ14), mild/none (nZ1); nuclear pleomorphism moderate/marked (nZ13), mild/none (nZ2); nuclear membrane irregularities moderate/marked (nZ6), mild/none (nZ9); nucleoli: mixture of single and multiple (nZ15); diffusely present (nZ15); mitoses absent (nZ15). Cell blocks of epithelial cells detected in 4 samples found P53 and Ki-67 stains to be negative. Salpingectomy specimens available in 3 patients documented benign histopathologic findings. Conclusions: Nuclear overlap, nuclear pleomorphism, prominent single nucleoli, multiple nucleoli, and background granular debris are all common findings encountered when reviewing direct experimental in vivo fallopian tube brushings from benign specimens. With experience, these cytologic findings should not be misinterpreted as suspicious or malignant.

Cytologic Findings on Experimental In Vivo Fallopian Tube Brush Specimens

Introduction: High grade tubo-ovarian serous adenocarcinoma is a significant cause of mortality. In recent years attention has turned to the fallopian tube as a primary source of precursor neoplastic lesions. The cytologic features of fallopian tube brushings from low risk patients have not been well described in modern cytology literature. Material and Methods: We describe the cytomorphologic features of tubal epithelium from prospectively collected experimental in vivo brushings of normal fallopian tubes from low risk patients. Both ThinPrep slides and cell blocks were prepared and reviewed in all specimens. P53 and Ki-67 immunostains were also performed when epithelial cells were detected in cell block specimens. Available follow-up histopathologic salpingectomy material was also reviewed. Results: A total of 15 specimens were obtained from 7 patients, ten collected by laparoscopy, 4 by hysteroscopy, and one after hysterectomy and bilateral salpingo-oophorectomy on an ex-vivo specimen. Cytologic findings were as followscellularity: moderate to high (nZ13), low (nZ2); background: granular debris (nZ10), clean (nZ4), blood (nZ1); architecture: mixture of clusters and single cells (nZ11), clusters (nZ3); nuclear overlap: moderate/marked (nZ14), mild/none (nZ1); nuclear pleomorphism moderate/marked (nZ13), mild/none (nZ2); nuclear membrane irregularities moderate/marked (nZ6), mild/none (nZ9); nucleoli: mixture of single and multiple (nZ15); diffusely present (nZ15); mitoses absent (nZ15). Cell blocks of epithelial cells detected in 4 samples found P53 and Ki-67 stains to be negative. Salpingectomy specimens available in 3 patients documented benign histopathologic findings. Conclusions: Nuclear overlap, nuclear pleomorphism, prominent single nucleoli, multiple nucleoli, and background granular debris are all common findings encountered when reviewing direct experimental in vivo fallopian tube brushings from benign specimens. With experience, these cytologic findings should not be misinterpreted as suspicious or malignant.

Infiltrative acute myeloid leukaemia as a cause of acute kidney injury.

A 75-year-old male was admitted for investigation of acute kidney injury. His medical history was significant for hypothyroidism and transfusion-dependent myelodysplastic syndrome. A bone marrow biopsy 1 month prior to admission had categorized him as having refractory anaemia with excess blasts (RAEB) Stage-II. His medications included thyroxine, cholecalciferol and the cytotoxic agent azacitadine. Over the preceding 6 months, he had noticed progressive lethargy, loss of weight and functional decline. Examination was unremarkable. Biochemistry demonstrated a serum creatinine level of 350 µmol/L, which had markedly worsened over 2 months. This was associated with 1.06 g/day proteinuria but no haematuria. Haematology showed normocytic anaemia (Hb 70 g/L), thrombocytopaenia (Plt 48 × 109/L) and marked leucocytosis (WCC 38.8 × 109/L). Dysplastic changes and occasional blasts were noted on the blood film (Figure 1). Serum protein electrophoresis, uric acid, autoimmune studies, hepatitis and HIV serology were unremarkable. Ultrasound demonstrated normal-sized kidneys of normal echogenicity and no evidence of obstruction. Fig. 1. May–Grunwald–Giemsa staining of the peripheral blood film shows pleomorphic population of blasts with an open chromatin and high nuclear:cytoplasmic ratio (thick arrows). Dysplastic neutrophils are also noted with abnormal segmentation ... A renal biopsy was performed, which showed renal cortex with heavy infiltration of atypical cells within the interstitium and lumina of small vessels. These cells had irregular nuclear membranes, prominent nucleoli and granular cytoplasm, and showed positive immunoperoxidase staining with myeloperoxidase, confirming the diagnosis of acute myeloid leukaemia (AML) with renal infiltration (Figures 2 and ​and33). Fig. 2. Highly cellular infiltration in the renal interstitium, atypical myeloid blasts with irregular nuclear membranes, prominent nucleoli and granular basophilic cytoplasm (H&E ×200). Fig. 3. Positive immunohistochemical staining for myeloperoxidase (MPO IHC ×100). A repeat bone marrow biopsy was subsequently performed which showed transformation into AML. The cause of the progressive kidney dysfunction was thus attributed to renal infiltration from AML. In view of the patient's poor prognosis and functional state, community-based palliative care was instituted. He passed away several weeks later. Malignant infiltration of the kidneys as a cause of renal failure has been well described [1–3]. The commonest causes are low-grade non-Hodgkin's lymphoma and acute lymphocytic leukaemia [4]. AKI due to diffuse kidney infiltration from AML has been reported in the setting of other precipitants [5]. Our case is unique, in that it demonstrates acute kidney injury resulting directly from malignant infiltration of renal parenchyma from AML. Conflict of interest statement. None declared.

Cytomorphological features of metastatic squamous cell carcinoma in serous effusions

To study the cytomorphological features of squamous cell carcinoma (SCC) in serous effusions. Conventional smears from 23 SCC were reviewed for the following features: cellularity, single cells, cell clusters, long cords, squamous pearls, cell-in-cell, 'windows', polygonal cells, anucleated cells, tadpole cells, fibre cells, third-type cells, refractile cytoplasmic ring, two-tone cytoplasm, cytoplasmic density, cytoplasmic vacuoles, signet ring cells, nuclear/cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleolus, anaplastic cells and mitosis. Subsequently, we also reviewed 15 reactive mesothelium, 18 mesotheliomas and 24 adenocarcinomas for comparison. Most SCC smears comprised mixed populations of single cells and cell clusters. Keratinized squamous cells and squamous pearls were diagnostic for well-differentiated SCC. Squamous eddies, appreciated on the cell block sections appearing as two-dimensional cell clusters with a swirling pattern, were characteristic for SCC. Poorly differentiated/third-type cells with atypical cytoplasmic keratinization, manifest as two-tone cytoplasm with a well-defined border and occasionally a refractile central ring, were an important clue for the squamous origin of the cells. Features including cell-in-cell, cytoplasmic vacuolation, double or multinucleated cells, anaplastic cells and mitotic figures were present in various degrees, and were not of diagnostic value. Certain cytological features are diagnostic for SCC, whereas other features of poorly differentiated SCC often overlap with those of reactive mesothelial cells, mesothelioma, metastatic adenocarcinoma or urothelial carcinoma in serous effusions. The combination of clinical history, appropriate immunohistochemical panel and cytomorphological features are important to ensure a correct diagnosis.

Rapid on‐site evaluation by endosonographer during endoscopic ultrasound‐guided fine needle aspiration for pancreatic solid masses

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is an established diagnostic method for patients with suspected pancreatic ductal carcinoma. Rapid on-site evaluation (ROSE) has been reported to improve the accuracy. However, an on-site cytopathologist is not routinely available in many institutions. One of the solutions may be ROSE by endosonographer. The aim was to examine whether diagnostic accuracy increases through ROSE by endosonographer using our cytological criteria. Patients who underwent EUS-FNA of solid pancreatic masses from January 2006 to August 2009 (n = 53, period 1) and September 2009 to April 2011 (n = 85, period 2) were retrospectively identified. Before initiating ROSE at the start of period 2, two endosonographers underwent training for cytological interpretation, which was focused on four cytological features of pancreatic ductal carcinoma: anisonucleosis, nuclear membrane irregularity, overlapping, and enlargement. During EUS-FNA in period 2, endosonographers classified the Diff-Quik smears under three atypical grades and evaluated the adequacy. All diagnoses were made by one pathologist without knowledge of clinical information. The rate of "inconclusive" diagnoses, interpreted as "suspicious," "atypical," and "inadequate for diagnosis" was reduced from 26.4% in period 1 to 8.2% in period 2 (P = 0.004). Moreover, diagnostic accuracy was increased from 69.2% in period 1 to 91.8% in period 2 (P < 0.001). This cytological grading system used in ROSE by endosonographers is invaluable for the diagnosis of pancreatic solid masses.

Usefulness of circulating tumor cell detection in pancreatic adenocarcinoma diagnosis.

157 Background: For pancreatic tumor, guidelines recommend pancreatic cytology examination by EUS-FNA as the first diagnostic procedure in unresectable patients. Detecting CTCs in blood could play the role of a “liquid biopsy”. The usefulness of CTC detection in the clinical management of these patients has not been established yet. Here, we aimed to prospectively evaluate the accuracy of a diagnostic method based on CTC detection. Methods: All patients referred from January 2011 to March 2012 for EUS-FNA procedure in a context of pancreatic solid tumor diagnosis were prospectively enrolled after their consent. Prior EUS-FNA procedure a sample of peripheral blood was collected. CTCs were analyzed using the ScreenCell method. Cells were considered as tumoral if they met these morphological criteria: nuclear diameter &gt;14 µ, anisocytosis, anisocaryosis, nuclear membrane irregularities, large nucleolus, clots of tumoral cells with platelets and fibrin. All analysis was performed by a pathologist blinded to the EUS-FNA results. The diagnosis of pancreatic adenocarcinoma was defined either by pathological evidence based on FNA or surgical specimen, or by clinical outcome with metastatic evolution and CA19.9 serum level rather than 10 fold normal value. Results: A total of 40 patients were included. A pancreatic adenocarcinoma was confirmed in 27/40 patients (68.3%). In 21 of the 27 patients, pathological proof of adenocarcinoma was obtained by EUS-FNA. For the diagnosis of adenocarcinoma, sensitivity and specificity of EUS-FNA were 77.8% and 100% respectively. The diagnostic accuracy of FNA was 85%. CTC detection was positive in 15 patients. Sensitivity and specificity were 55.5% (CI95% [40.1%; 70.9%]) and 100% (CI95% [75%; 100%]) respectively. The diagnostic accuracy of CTC was 70%. Metastatic statuses, lymph node involvement, vascular invasion, size of tumor and CA19.9 serum level were not statistically associated with CTC detection. Conclusions: We suggest that CTC detection be applied as first-line procedure before EUS-FNA in the strategy of pancreatic tumor diagnosis. With the implementation of this blood test on a routine basis, approximately one half of these patients could avoid invasive EUS-FNA procedure.

Image analysis of hyperchromatic crowded cell groups in SurePath cervical cytology

The discrimination of hyperchromatic crowded cell groups (HCCGs) in cervical cytology is a difficult and error-prone interpretive task. While the classic features of dyskaryosis are of undoubted value, the contribution of size, shape and colour intensity of HCCGs is less certain. This study employed morphometric analysis to determine whether HCCG area, shape and colour intensity are useful in categorising them. Seventy-five digital images from each of six categories of HCCG were subjected to image analysis. Ten variables relating to HCCG size, shape and colour intensity were assessed by discriminant function analysis. A further 28 cases were employed as a test set to determine the classification accuracy of the discriminant model. All samples were SurePath liquid-based cytology preparations. Nine of the 10 variables contributed significantly to the model (P<0.001) but no single variable had sufficient discriminative ability. Classification accuracy was highest for abnormal endocervical HCCGs and lowest for squamous metaplastic cells (64.0 vs. 17.3% correct classification rate). The accuracy of the model for distinguishing normal and abnormal HCCGs was 70.0%, which was significantly higher than chance (P<0.0001), but this reduced to 64.3% for the test cases, which was no better than chance (P>0.05). The area, shape and colour intensity of HCCGs, either alone or in combination, have little discriminative value. Practitioners and trainers should focus on the well-established features of dyskaryosis, such as chromatin pattern, nuclear membrane irregularities and group architecture. In terms of morphometric analysis, DNA ploidy and chromatin texture analysis may be more fruitful avenues of investigation.

Cytological Findings of the Micropapillary Variant of Urothelial Carcinoma: A Comparison with Typical High-Grade Urothelial Carcinoma

BackgroundMicropapillary variant of urothelial carcinoma (MPUC) showed distinct pathologic features and aggressive behavior. The cytologic findings of MPUC are still indistinct. In this study, we evaluated the cytological findings of MPUC compared with those of high-grade urothelial carcinoma (HGUC).MethodsThe voided urine cytology of 8 cases of MPUC and 8 cases of HGUC was reviewed. Following cytological parameters were evaluated: cellularity, background, number of small, tight papillary clusters, small acinar structure, scattered single cells, cytoplasmic features, nuclear-to-cytoplasmic ratio, nuclear pleomorphism, nuclear membrane irregularity, hyperchromasia, chromatin pattern and nucleoli.ResultsCompared to that of HGUC, cytology of MPUC showed large numbers of small, tight papillary clusters, small acinar structure, few numbers of single cells, and hyperchromatic nuclei. Other parameters were similar between the two groups; both groups showed similar cellularity, dense or vacuolated cytoplasm, moderate to severe nuclear pleomorphism, irregular nuclear membrane, coarse granular chromatin, and small and prominent nucleoli.ConclusionsThe urine cytology of MPUCs showed smaller and tighter papillary cell clusters, more small acinar structures, fewer numbers of scattered single cells, and more hyperchromatic nuclei than that of HGUC. These features can help to distinguish MPUC and HGUC and offer an early cytological diagnosis of MPUC.

Role of biliary tract cytology in the evaluation of extrahepatic cholestatic jaundice

Background:Endoscopic evaluation is critical in assessing the cause of obstructive jaundice. Cytological techniques including bile aspiration and biliary brushings have become the initial diagnostic modality.Aim:The aim of this study is to evaluate the role of endoscopic biliary tract cytology as a diagnostic tool in the evaluation of extrahepatic cholestatic jaundice.Materials and Methods:A total of 56 biliary tract specimens including 34 bile aspirations and 22 biliary brushings from 41 consecutive patients who had presented with obstructive jaundice and underwent endoscopic retrograde cholangiopancreatography (ERCP) were assessed by cytological examination. The smears prepared were analyzed for standard cytological features.Results:Cytologic diagnosis was adenocarcinoma in 13 (31.7%) cases, atypical in 2 (4.9%), reactive in 3 (7.3%) and benign changes in 19 (46.3%) cases. 4 (9.8%) cases were non-diagnostic. Serum bilirubin was significantly elevated in the malignant group. Biliary stricture was the most common finding on ERCP (68.3%). On cytological examination, presence of solitary, intact atypical cells, enlarged nuclei, irregular nuclear membrane, coarse chromatin and nucleoli were important cytologic criteria for differentiating malignant from benign biliary specimens.Conclusions:Regular use of bile cytology and brushings during ERCP evaluation of extrahepatic cholestatic jaundice is invaluable in obtaining a morphologic diagnosis. A systematic approach, use of strict cytomorphologic criteria and inclusion of significant atypia as malignant diagnosis may improve the sensitivity.

Antiretroviral Therapy–associated Coccidioidal Meningitis

Antiretroviral Therapy–associated Coccidioidal Meningitis

Response of the common cutworm Spodoptera litura to zinc stress: Zn accumulation, metallothionein and cell ultrastructure of the midgut

By exposing the common cutworm Spodoptera litura Fabricius larvae to a range of Zinc (Zn) stress, we investigated the effects of dietary Zn on Zn accumulation, metallothionein (MT), and on the ultrastructure of the midgut. The techniques we used were inductively coupled plasma-atomic emission spectrometer (ICP-AES), real-time PCR combined with cadmium-hemoglobin total saturation, and transmission electron microscopy (TEM), respectively. There was a significant dose–response relationship between the Zn accumulations in the midgut of the larvae and the Zn concentrations in the diet. Furthermore, both MT content and MT gene expression in the midgut were significantly induced in the 50–500mgZn/kg treatments, and were significantly positively correlated with the Zn accumulations in the midgut. When S. litura larvae were fed with the diet treated with 500mg Zn/kg, Zn accumulation and MT content in the midgut was 4450.85mgZn/kg and 372.77mg/kg, respectively, thereafter there was a little increase; the level of MT gene expression was maximal, thereafter there was a sharp decrease. TEM showed that numerous electron-dense granules (EDGs) and vacuoles appeared in the cytoplasm of the midgut cells, their number and size being closely correlated with the Zn accumulations in the midgut. Moreover, the nuclei were strongly influenced by Zn stress, evidenced by chromatin condensation and irregular nuclear membranes. Therefore, after being exposed to Zn in the threshold (500mgZn/kg) range, S. litura larvae could accumulate Zn in the midgut, which led to the induction of MT and changes in cell ultrastructure (mainly the presence of EDGs). The induction of MT and precipitation of Zn in EDGs may be the effective detoxification mechanisms by which the herbivorous insect S. litura defends itself against heavy metals.

Fine‐needle aspiration of gray zone lesions of the breast: Fibroadenoma versus ductal carcinoma

While breast lesions have characteristic cytological features, some lesions, particularly adenocarcinoma and fibroadenoma, may present with overlapping features causing erroneous diagnoses. The current study aimed to define significant cytomorphologic features predictive of fibroadenoma and adenocarcinoma, respectively. Further, we intended to evaluate the predictive characteristics for differentiation between gray zone lesions and to identify root causes contributing to misdiagnoses. First, direct smears prepared from 14 histology-confirmed fibroadenomas and 14 adenocarcinomas were reviewed and characteristics of commonly encountered morphologic features were assessed. We then retrospectively and blindly reviewed nine cytohistologic discrepant cases using the significant characteristic as a guideline, in order to assess whether these discrepant cases could be correctly categorized. Morphologic characteristics predictive of fibroadenoma included moderate cellularity, large, folded cellular sheets/aggregates, staghorn projections, smooth and round borders, monolayers, honeycomb arrangement, smaller nuclear size, and background bipolar cells. Predictive characteristics of adenocarcinoma included high cellularity, loose cohesive sheets/aggregates, pointed projections, irregular borders, larger nuclear size, irregular nuclear membrane, prominent nucleoli, and single atypical epithelial cells. Retrospective, blind review correctly re-classified seven out of nine cytohistologic discrepant cases, including five false negative cases and two false positive cases. Root causes contributing to the misdiagnoses were large branching sheets of carcinoma mimicking folded sheets of fibroadenoma; fibroblasts mimicking myoepithelial cells; apocrine cells mimicking carcinoma cells; and not recognizing the loose myxoid matrix presenting as soap bubbles in fibroadenoma. In conclusion, this study identified significant characteristics that can assist in achieving accurate diagnosis in a subpopulation of breast aspirates that present with overlapping features.

Cytomorphologic features of metastatic urothelial carcinoma in serous effusions

Metastatic urothelial carcinoma (UC) to serous effusion (SE) is extremely rare and its cytomorphological features have only been described in case reports. In this study, we searched the pathology database at University of Michigan for SEs due to metastatic UC in the last 20 years. A total of 25 cases from 20 patients with clinically and pathologically confirmed metastatic UC in SEs were retrieved. The specimens consisted of 15 pleural, 8 peritoneal, and 2 pericardial effusions. Smears were reviewed and evaluated for the following features: cellularity, single cells, cell clusters or short cords, cell wrapping, "windows" between the cells, two-tone cytoplasm, cytoplasmic vacuoles, signet ring cells, nuclear to cytoplasmic (N/C) ratio, nuclear hyperchromasia, irregular nuclear membrane, nuclear centricity, double or multiple nuclei, nucleoli, anaplastic cells and mitosis. Our results showed that UC manifested in SEs predominantly as a single cell population with or without clusters or short cords, and frequently exhibited the "cell wrapping" of two or more cells. Individual UC cell in SEs exhibited nuclear enlargement with increased N/C ratio, irregular nuclear membranes, hyperchromatic coarse chromatin and frequently prominent nucleoli. Double or multinucleated cells, cells with vacuolated cytoplasm or signet ring appearance were also frequently present. Our results demonstrated that while certain features could suggest the diagnosis of UC, the cytomorphological features are not specific and often overlap with those of reactive mesothelium, mesothelioma, metastatic adenocarcinoma, or squamous cell carcinoma in SEs. Accurate diagnosis of UC rests on the combination of clinical history, cytomorphologic features and appropriate immunohistochemical panel.

Intraductal tubulopapillary neoplasm of the pancreas on fine needle aspiration: Case Report with Differential Diagnosis

Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.