Angioimmunoblastic T-Cell Lymphoma Diagnosed From Serous Effusion by Integration of Cytologic Features and Ancillary Studies.

OBJECTIVES: To explore the approach to the diagnosis of malignant serous effusion (SE) caused by angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinical, cytomorphologic, immunophenotypic, and molecular features of 6 patients were summarized. RESULTS: Clinically, SE caused by AITL was predominant in middle-aged and older male patients with multiple SEs and lymphadenopathy. Cytomorphology showed small to medium-sized, irregular lymphocytes with clear cytoplasm and mixed with various inflammatory cells and apoptosis. Hodgkin/Reed-Sternberg-like cells were detected in 2 of 6 cases. Furthermore, 2 patterns of cytomorphology were described for the first time. Flow cytometry revealed abnormal T-cell populations with loss of surface CD3 (3/4 cases) and CD7 (3/4 cases). In addition, B-cell populations lacking surface immunoglobulin (Ig) were identified in 2 of 4 cases. Immunocytochemical staining revealed expression of at least 2 T follicular helper markers. Epstein-Barr virus-encoded RNA (EBER)-positive cells were demonstrated in 4 of 5 cases. Clonal T-cell receptor γ chain rearrangement was detected in 6 cases, and 3 of them had concomitant clonal immunoglobulin gene rearrangement. Moreover, 2 cases revealed discrepant findings regarding IgH/Igκ rearrangements in cytohistologic correlation. CONCLUSIONS: This study broadens the morphologic spectrum of malignant SE caused by AITL and provides diagnostic criteria in routine practice.

Diagnosis of steatohepatitis and fibrosis in biopsy-proven nonalcoholic fatty liver diseases: including two-dimension real-time shear wave elastography and noninvasive fibrotic biomarker scores.

Background: The aim of this retrospective study was to evaluate the accuracy of two-dimension real-time shear wave elastography (2D-SWE) for the diagnosis of steatohepatitis and fibrosis in a cohort patients confirmed nonalcoholic fatty liver diseases (NAFLD) by liver biopsy, and compare with four noninvasive fibrotic biomarker scores (NFS, FIB-4, BARD and APRI). Methods: 116 NAFLD patients and 23 normal control group were enrolled. The diagnostic performance of 2D-SWE and four noninvasive fibrotic biomarker scores was evaluated based on histopathological inflammation grades and fibrosis stages (F) according to Kleiner/Brunt et al.'s criteria classification. 5-fold cross validation and receiver operating characteristics curve (ROC) analyses were used to obtain an assessment of 2D-SWE and four noninvasive fibrotic biomarker scores; then cross validated area under the curves (AUCs) were compared using the test of Delong. Meanwhile, influence of steatosis on liver stiffness measurement (LSM) of 2D-SWE was also studied. Results: Liver stiffness measured by 2D-SWE proved to be an excellent diagnostic indicator for detecting steatohepatitis (AUROC =0.88), and fibrosis: ≥F2 stage (AUROC =0.86), ≥F3 stage (AUROC =0.89) and =F4 stage (AUROC =0.90) with the cutoff values were 7.3, 10.0, 11.6 and 12.6 kPa, respectively. Compared with fibrotic scores, 2D-SWE had the highest AUROC for predicting ≥F2, ≥F3, =F4 by Delong test (all P<0.05). No statistic differences of LSM were found among different steatosis levels (P=0.97). Conclusions: The stiffness measured by 2D-SWE could be used to noninvasively identify steatohepatitis and stage fibrosis in NAFLD patients. Moreover, the diagnosis efficiency of the stiffness measured by 2D-SWE could not be influenced by steatosis.

Serous Effusions Diagnostic Accuracy for Hematopoietic Malignancies: A Cyto-Histological Correlation.

Background: The aim of this study was to establish the liability of cytological diagnostic and, along with ancillary techniques, to sub-classify hematopoietic malignancies in serous effusions. Methods: We retrospectively reviewed the serous effusions of hematopoietic malignancies over an 11-year period, along with ancillary studies, clinical and histological data. We compared cytological along with histological diagnosis to evaluate the value of cytology itself. Furthermore, the discrepant cases were reviewed. Results: In this study, a total of 242 cases were identified as hematopoietic malignancies. Ancillary technologies were performed: in 24 cases FCM, 242 cases ICC, 35 cases ISH, 81 cases PCR and 10 cases FISH. Cyto-histological correlation was available for 122 cases. The subtyping of hematopoietic malignancies was achieved using cytological material in 65/122 cases (53.3%). Of the 65 cases, T-Acute lymphoblastic leukemia/lymphoma (22.1%) was the leading subtype, followed by Burkitt lymphoma (5.7%), plasmacytoma (5.7%). Cyto-histological correlation showed a 100% concordant rate of diagnosis for hematopoietic malignancies and a high degree of agreement on sub-classification (51.6%). In this regard, T-acute lymphoblastic leukemia/lymphoma, plasmacytoma, extranodal NK/T-cell lymphoma, nasal type, anaplastic large cell lymphoma, myeloid sarcoma, and follicular lymphoma showed the highest degree of agreement (100%). The sub-classification on cytology was achieved in 53 out of the remaining 120 cases without histological diagnosis (44.2%). T-acute lymphoblastic leukemia/lymphoma (20.8%) was again the most frequently encountered subtype, followed by plasmacytoma (5.8%) and Burkitt lymphoma (4.2%). Conclusions: This large series study provided evidence that combining cytology and ancillary studies enabled the accurate serous effusions cytological diagnoses and subsequent sub-classification for the described malignancies.

Contrast-Enhanced Ultrasound in the Differential Diagnosis of Primary Thyroid Lymphoma and Nodular Hashimoto's Thyroiditis in a Background of Heterogeneous Parenchyma.

OBJECTIVE: To investigate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the differentiation of primary thyroid lymphoma (PTL) and nodular Hashimoto's thyroiditis (NHT) in patients with background of heterogeneous diffuse Hashimoto's thyroiditis (HT). METHODS: Sixty HT patients with 64 thyroid nodules (31 PTL and 33 NHT) who had undergone CEUS examination were included in this study. With histopathological results as the reference, we evaluated the imaging features of each nodule on both conventional ultrasonography (US) and CEUS. Quantitative CEUS parameters including peak intensity (PI), time to peak (TTP), and area under the time-intensity curve (AUC) were gathered in the nodule and background parenchyma. The ratio indexes of theses parameters were calculated by the ratio of the lesion and the corresponding thyroid parenchyma. Logistic regression and receiver operating characteristic (ROC) curves analyses of valuable US indicators were further preformed to evaluate the diagnostic capability of CEUS in discrimination of PTL and NHT. RESULTS: Among all the observed US imaging features and CEUS parameters, 10 indicators showed significant differences between PTL and NHT (all P < 0.05). All the significant indicators were ranked according to the odds ratios (ORs). Eight of them were CEUS associated including imaging features of enhancement pattern, degree, homogeneity, and quantification parameters of PI, AUC, ratios of PI, AUC, and TTP, while indicators on conventional US, including vascularity and size ranked the last two with ORs less than 3. The five single CEUS parameters showed good diagnostic performance in diagnosis of PTL with areas under ROC curves of 0.72-0.83 and accuracies of 70.3-75.0%. The combination of CEUS imaging features and the ratios of PI, AUC, and TTP demonstrated excellent diagnostic efficiency and achieved area under ROC curve of 0.92, which was significantly higher than any of the five single parameters (all P < 0.05), with a sensitivity of 83.9%, specificity of 87.9%, and accuracy of 85.9%. CONCLUSIONS: CEUS is an efficient diagnostic tool in the differential diagnosis of PTL and NHT for patients with diffuse HT. Conjoint analysis of CEUS imaging features and quantification parameters could improve the diagnostic values.

The accuracy of diagnosing Burkitt lymphoma in serous effusion specimen: A cytological-histological correlation with ancillary studies.

OBJECTIVE: The objective of this study is to evaluate the effectiveness of diagnosing Burkitt lymphoma (BL) in serous effusion (SE) specimen and summarise the characteristics of BL in SE. We also assess the utility of a germinal centre-associated marker, LMO2, in the differential diagnosis of BL in SE specimens. METHODS: Eleven cases of malignant SE caused by BL were reviewed. SE cytology and histological biopsy diagnoses were compared to determine the concordance rates. RESULTS: A uniform population of non-cohesive medium-sized lymphoid cells with frequent apoptosis was found on SE smears or cell block sections. Cytoplasmic and nuclear vacuoles presented in seven cases. Immunophenotyping demonstrated positivity for CD79a (three of three cases), CD10 (seven of 11 cases), BCL6 (nine of 11 cases), MUM-1 (one of nine cases), CD20 and MYC (11 cases). LOM2 was negative in nine of nine cases. Both IGH/MYC rearrangement and MYC rearrangement were identified in four of six cases, and two of six cases carried isolated MYC rearrangement or isolated IGH/MYC rearrangement, respectively. The diagnoses of eight BLs and three B-cell non-Hodgkin lymphomas were established according to cytomorphology and ancillary studies. SE cytology provided initial pathological diagnoses for eight cases (six BLs and two non-Hodgkin lymphomas). Histodiagnoses were available for eight cases. The concordance rate of cytological-histological diagnosis was 62.5% (five of eight cases). CONCLUSIONS: Combining cytomorphology and ancillary studies enables the accurate diagnosis of BL in SE specimens. Furthermore, LMO2 may be a useful marker in the differential diagnosis of BL.

Metastatic brain carotid body paraganglioma with endocrine activity: a case report and literature review.

A woman with hypertension and hyperglycemia was diagnosed a metastatic brain carotid body paraganglioma. Her blood pressure, glucose, and norepinephrine were normal after craniotomy. Although most carotid body tumors are benign, a few show distant metastasis. This is the first reported case of intracerebral metastases from a carotid body tumor.

Mediastinal type B3 thymoma combined with germ cell tumor: cytologic diagnosis.

Primary mediastinal thymoma combined with germ cell tumor (GCT) is extremely rare, and is likely to be misdiagnosed. Here we report a case of mediastinal type B3 thymoma combined with seminoma in which the seminoma component was missed by histologic examination and initially diagnosed by using a pleural effusion sample. The patient was a 46 year old male with chest distress, cough, and supraclavicular lymph node enlargement. A large anterior mediastinal mass was revealed by diagnostic imaging. The tumor was completely removed by thoracotomy. Grossly, a solid mass about 10 cm × 8 cm × 5 cm with cystic degeneration was found. Histologic examination revealed Type B3 thymoma accompanying with multiple lymph node metastases. One year later, CT scan found an irregular mass on the right side of anterior-superior mediastinum with a large amount of effusion in the right side pleural cavity. Cytologic examination and immunostains of the pleural effusion sample revealed metastatic seminoma. Then the original surgical sample was reviewed and the seminoma component also was found besides the thymoma. To the best of our knowledge, this is the first description of type B3 thymoma combined with seminoma, diagnosed by histology and pleural effusion together. We also present a literature review.

Liquid-Based Cytopathology Test: A Novel Method for Diagnosing Pulmonary Mucormycosis in Bronchial Brushing Samples.

Background: Pulmonary mucormycosis, a relatively rare but severe pulmonary fungal disease with a high mortality rate, is difficult to diagnose in immunocompromised patients. Conventional cytopathology (CCP) examination of respiratory samples can help detect Mucorales, but its diagnostic sensitivity is poor. The aim of this study was to assess the first application of liquid-based cytopathology test (LCT) to detect Mucorales. Methods: A total of 33 pairs of bronchial brushing samples from 27 patients diagnosed as pulmonary mucormycosis by fiberoptic bronchoscopy biopsy were prepared as slides using both CCP and LCT. LCT and CCP used the same cytology brush to obtain samples at the same site during the same time as the fiberoptic bronchoscopy biopsy. All samples were stained with Papanicolaou, GMS and PAS. CCP and LCT slides were evaluated from the rate of positive detection, 8 cytomorphological features and 7 background features. Results: LCT-prepared slides showed a higher positive rate of Mucorales detection than CCP-prepared slides for Papanicolaou's staining [28/33 (84.85%) vs. 15/33 (45.45%), p = 0.001] and for "special staining" with GMS and PAS [29/33 (87.88%) vs. 18/33 (54.55%), p = 0.003]. Clearer smear background and more distinct stereoscopic cytopathological features were observed in LCT. Messy yarn-like necrosis observed in conventionally prepared 75.76% (25/33) samples was cytomorphological suggestive for the diagnosis of mucormycosis. Conclusion: This retrospective study suggests that LCT may be better than CCP to detect Mucorales in bronchial brushing samples from patients with pulmonary mucormycosis.

Fine needle aspiration of giant cell tumor involving thyroid gland: A case report of an unprecedented entity.

Fine-needle aspiration (FNA) is commonly used to evaluate both primary thyroid lesions (PTLs) and secondary thyroid neoplasms (STNs). Although STNs are uncommon, metastases from various primary sites particularly the kidney, lung, and breast have been previously described. Giant cell tumor (GCT) is typically found in the metaphyseal-epiphyseal area of long bones that seldom involves thyroid. The typical cytological feature of GCT on FNA smears is highly cellular dual cell pattern consisting of mononuclear stromal cells and multinucleate osteoclast-like giant cells. By performing FNA of the left lobe of thyroid and clinico-radiological evaluation, we were able to diagnose a mass in a 40-year-old male patient as GCT based on cytological specimen. To the best of our knowledge, this is the first case that a GCT is identified in the thyroid gland by FNA initially.

Targeted next-generation sequencing in cytology specimens for molecular profiling of lung adenocarcinoma.

AIMS: Molecular profiling is important for cancer diagnosis and treatment. For many advanced stage lung cancer patients, cytology specimens may be the only materials available for molecular testing. The aim of this study is to evaluate the utility of Next-Generation Sequencing (NGS) of cytology specimens for the molecular profiling of lung adenocarcinoma. METHODS: NGS was performed on cell blocks of pleural effusions and fine-needle aspiration (FNA) samples of lung adenocarcinoma to determine the mutation status of EGFR, KRAS, PIK3CA, BRAF, ALK, PDGFRA, and DDR2. Then, quantitative Real-Time PCR (qPCR) was performed and the results were compared to those of NGS. Next, NGS was performed on available histological specimens from the same patients. Last, DNA Quality Index analysis was performed to further explore the applicability of using cytology samples as the source for NGS. RESULTS: NGS detected mutations in EGFR, PIK3CA, and KRAS. NGS and qPCR results showed high concordance. NGS exhibited advantages over qPCR in detecting non-hotspot mutations and providing accurate information for allele sequence and mutation frequency. NGS of cytological and histological samples from the same patients showed high concordance. DNA Quality Index analysis showed that DNA extracted from cell blocks of pleural fluid was of similar quality compared to FFPE tissue blocks. CONCLUSIONS: NGS can be successfully performed on both FNA and pleural fluid samples from lung adenocarcinomas. The high quality DNA of FFPE cell block of pleural effusion makes it the first choice for molecular profiling, especially when cytology specimens are the only available samples for molecular profiling.

Clinical and pathological characteristic of metastatic malignant mesothelioma initially diagnosed by lymph node biopsy.

BACKGROUND: It is a great challenge for pathologists to initially diagnose metastatic malignant mesothelioma (MM) by the lymph node biopsy without any history of primary MM. Because the onset of MM is hidden and the metastatic MM in lymph node is relatively uncommon. Besides, morphologic and immuohistochemistry features of MM are similar to other tumors. METHODS: In order to improve the initial diagnostic accuracy of metastatic MM from LN biopsy and to reduce or avoid the possibility of missed diagnosis or misdiagnosis, we had collected the clinical and pathological data of the metastatic MM cases in our department, and summarized the characteristics of morphological, immunohistochemical and fluorescence in situ hybridization (FISH) results. RESULTS: Seven patients (4 males and 3 females) with 21-73 year-old had been included in our study. Six cases showed serous cavity effusion, serosal thickening and systemic multiple lymph node enlargement. The "moderate, nice" tumor cells were arranged in variable patterns. Mitosis was hardly to be found and necrosis was absent. Four immunohistochemical staining panels and FISH detection had been used for diagnosis and differential diagnosis of MM. All cases expressed broad-spectrum epithelial markers and at least 2 mesothelial-cell-origin markers. None were positive for specific-tissue-origin markers, and all cases were diagnosed of malignancy according to immunohistochemical markers and detection of pl6 gene deletion. CONCLUSION: It is necessary for us to keep our awareness of metastatic MM in lymph node. Correct diagnosis of MM metastasis by lymph node biopsy were based on detailed understanding of the clinical manifestation and the image data, careful observation of morphologic characteristics, and properly using immunohistochemical markers or FISH detection if necessary for diagnosis and differential diagnosis.

Pancreatic metastasis resulting from thymic neuroendocrine carcinoma: A case report.

Thymic neuroendocrine carcinoma (NEC) is a rare type of cancer. Unlike other thymic epithelial tumors and carcinoids originating in other locations, thymic NEC possesses a more aggressive biological behavior, including invasion to proximal structures, local recurrence and distant hematogenous metastasis. Distant metastasis is often observed in the bones, lungs, spleen, liver and adrenal glands. However, pancreatic metastasis resulting from thymic NEC is extremely uncommon, and only a few cases of patients with this disease have been reported. The current study presents the case of a patient with pancreatic metastasis resulting from thymic NEC. The patient was admitted to hospital with an anterior mediastinal neoplasm, which was identified using chest enhanced computed tomography. The patient underwent a monobloc excision of the tumor with resection of involved structures. Subsequently, a pathological diagnosis of atypical thymic carcinoid was provided, according to the morphological characteristics observed and the expression of neuroendocrine markers, as identified by immunohistochemistry. Following surgery, the patient received adjuvant chemotherapy and radiotherapy. However, ~2 years after surgery, metastasis at the pancreatic head was identified. The patient underwent a total pancreatectomy and splenectomy, and did not receive any post-operative therapies; however, the patient succumbed to the disease 9 months following surgery. Overall, the results from the present study demonstrate the clinical features of thymic NEC, which may aid with the diagnosis of this rare disease in other patients.

Diagnostic Utility of Diffusion-weighted Magnetic Resonance Imaging in Differentiating Small Solid Renal Tumors (≤ 4 cm) at 3.0T Magnetic Resonance Imaging.

BACKGROUND: The aim of this study was to assess the performance of apparent diffusion coefficient (ADC) measurement obtained with diffusion-weighted magnetic resonance imaging (DW-MRI) to distinguish renal cell carcinomas (RCCs) from small benign solid renal tumors (≤ 4 cm). METHODS: In this cross-sectional study, 49 consecutive patients with histopathologically confirmed small solid renal tumors, and seven healthy volunteers were imaged using nonenhanced MRI and DW-MRI. The ADC map was calculated using the b values of 0, 50, 400, and 600 s/mm 2 and values compared via the Kruskal-Wallis and Mann-Whitney tests. The utility of ADC for differentiating RCCs and benign lesions was assessed using a receiver operating characteristic curve. Multiple nonenhanced MRI features were analyzed by Logistic regression. RESULTS: The tumors consisted of 33 cases of clear-cell RCCs (ccRCCs) and 16 cases of benign tumors, including 14 cases of minimal fat angiomyolipomas and 2 cases of oncocytomas. The ADCs showed significant differences among benign tumors ([0.90 ± 0.52] × 10-3 mm 2 /s), ccRCCs ([1.53 ± 0.31] × 10-3 mm 2 /s) and the normal renal parenchyma ([2.22 ± 0.12] × 10-3 mm 2 /s) (P < 0.001). Moreover, there was statistically significant difference between high and low-grade ccRCCs (P = 0.004). Using a cut-off ADC of 1.36 × 10-3 mm 2 /s, DW-MRI resulted in an area under the curve (AUC), sensitivity, and specificity equal to 0.839, 75.8%, and 87.5%, respectively. Nonenhanced MRI alone and the combination of imaging methods led to an AUC, sensitivity and specificity equal to 0.919, 93.9%, and 81.2%, 0.998, 97%, and 100%, respectively. The Logistic regression showed that the location of the center of the tumor (inside the contour of the kidney) and appearance of stiff blood vessel were significantly helpful for diagnosing ccRCCs. CONCLUSIONS: DW-MRI has potential in distinguishing ccRCCs from benign lesions in human small solid renal tumors (≤ 4 cm), and in increasing the accuracy for diagnosing ccRCCs when combined with nonenhanced MRI.

Two melodies in concert: mitral and pulmonary valve replacement late in repaired tetralogy of Fallot.

Disruption of pulmonary valve integrity after Tetralogy of Fallot repair often results in a cascade of hemodynamic and electrophysiological abnormalities. Here we report an uncommon case of severe pulmonary regurgitation with concomitant rheumatic mitral stenosis diagnosed 25 years after primary Tetralogy of Fallot repair. A 33-year-old man presented with symptomatic palpitation and exercise intolerance and was treated successfully with pulmonary and mitral valve replacement, after which his symptoms improved dramatically.