Browsing by Author "Department of Pathology and Laboratory Medicine, School of Medicine"
Now showing 1 - 10 of 18
Results Per Page
Sort Options
Item Classical gonadoblastoma: its relationship to the “dissecting” variant and undifferentiated gonadal tissue(Wiley, 2017) Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of MedicineClassical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development. Approximately 40% of such neoplasms are bilateral. Almost all gonadoblastomas occur in patients who have a Y chromosome or part thereof; testis specific protein Y-encoded 1 (TSPY1) is the putative gene. If a gonad in a patient who has a disorder of sex development contains germ cells with delayed maturation and also harbors the TSPY1 gene, the cells can undergo transformation to classical gonadoblastoma. The latter consists of rounded islands composed of germ cells, sex cord elements, and hyaline basement membrane material surrounded by a variably cellular gonadal stroma that sometimes contains steroid cells. Classical gonadoblastoma can be interpreted as a noninvasive neoplasm that is the precursor of germinoma, and, indirectly, other more aggressive germ cell neoplasms. Undifferentiated gonadal tissue is the precursor of classical gonadoblastoma and contains germ cells with delayed maturation that express octamer-binding transcription factor 4 (OCT4); however, other germ cells show normal maturation and express TSPY1. If all germ cells in a patient with undifferentiated gonadal tissue involute, the result is a secondary streak. Undifferentiated gonadal tissue is a non-neoplastic condition that should be clearly distinguished from “dissecting gonadoblastoma,” a neoplasm derived from classical gonadoblastoma that is the precursor of some germinomas. “Dissecting gonadoblastoma” is a variant of classical gonadoblastoma that has unusual growth patterns and contains both sex cord and germ cell elements. Clonal expansion of germ cells is a characteristic of the late stage of “dissecting gonadoblastoma”.Item Cutaneous Syncytial Myoepithelioma: A Recently Described Neoplasm Which May Mimic Nevoid Melanoma and Epithelioid Sarcoma(Wiley, 2017) Alomari, Ahmed K.; Brown, Noah; Andea, Aleodor; Betz, Bryan L.; Patel, Rajiv M.; Department of Pathology and Laboratory Medicine, School of MedicineCutaneous syncytial myoepithelioma is a recently described rare tumor of the dermis. It is derived and composed purely of myoepithelial cells and shows a characteristic syncytial growth pattern of neoplastic cells with little intervening stroma and no recognizable ductal structures. It represents a diagnostic challenge to dermatopathologists given its rarity and unusual immunophenotype. Molecular testing for rearrangement of the EWSR1 gene plays a significant role in confirming the diagnosis in most cases. Herein, we present 2 cases with mundane clinical presentations and challenging histopathological findings. In both cases, the lesion was composed of relatively well-circumscribed proliferation of epithelioid and spindle cells in the superficial dermis growing in a syncytial fashion and showing focal adipocytic metaplasia. The 2 cases had slightly different immunohistochemical profiles, but shared focal positivity for S100, EMA and pan-keratin or p63. Break-apart FISH demonstrated the presence of an EWSR1 gene rearrangement confirming the diagnosis in both cases. We discuss the most important differential diagnoses, particularly melanocytic lesions and epithelioid sarcoma and the original diagnostic considerations that the cases were referred to us with. We also review the molecular features and spectrum of immunohistochemical findings in these lesions and their role in excluding entities in the differential diagnosis.Item Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease(SpringerNature, 2017-04-27) Müller, Stephan; Preische, Oliver; Sohrabi, Hamid R.; Gräber, Susanne; Jucker, Mathias; Dietzsch, Janko; Ringman, Ralph N.; Martins, Ralph N.; McDade, Eric; Schofield, Peter R.; Ghetti, Bernardino; Rossor, Martin; Graff-Radford, Neill R.; Levin, Johannes; Galasko, Douglas; Quaid, Kimberly A.; Salloway, Stephen; Xiong, Chengjie; Benzinger, Tammie; Buckles, Virginia; Masters, Colin L.; Sperling, Reisa; Bateman, Randall J.; Morris, John C.; Laske, Christoph; Department of Pathology and Laboratory Medicine, School of MedicineThe relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aβ brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.Item Extranodal extension of lymph node metastasis influences recurrence in prostate cancer: a systematic review and meta-analysis(SpringerNature, 2017-05-24) Luchini, Claudio; Fleischmann, Achim; Boormans, Joost L.; Fassan, Matteo; Nottegar, Alessia; Lucato, Paola; Stubbs, Brendon; Solmi, Marco; Porcaro, Antonio; Veronese, Nicola; Brunelli, Matteo; Scarpa, Aldo; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of MedicineThe extranodal extension (ENE) of nodal metastasis involves the extension of neoplastic cells through the lymph node capsule into the perinodal adipose tissue. This morphological feature has recently been indicated as an important prognostic factor in various cancer types, but its role in prostate cancer is still unclear. We aimed to clarify it, performing the first meta-analysis on this issue, comparing prognostic parameters in surgically treated, node-positive prostate cancer patients with (ENE+) vs. without (ENE-) ENE. Data were summarized using risk ratios (RRs) for number of deaths/recurrences and hazard ratios (HRs), with 95% confidence intervals (CI), for the time-dependent risk related to ENE positivity. Six studies followed-up 1,113 patients with N1 prostate cancer (658 ENE+ vs. 455 ENE-) for a median of 83 months. The presence of ENE was associated with a significantly higher risk of biochemical recurrence (RR = 1.15; 95%CI: 1.03-1.28; I2 = 0%; HR = 1.40, 95%CI: 1.12-1.74; I2 = 0%) and "global" (biochemical recurrence and distant metastasis) recurrence (RR = 1.15; 95%CI: 1.04-1.28; I2 = 0%; HR = 1.41, 95%CI: 1.14-1.74; I2 = 0%). ENE emerged as a potential prognostic moderator, earmarking a subgroup of patients at higher risk of recurrence. It may be considered for the prognostic stratification of metastatic patients. New possible therapeutic approaches may explore more in depth this prognostic parameter.Item Fine-Needle Aspirates of Thyroid Microcarcinoma(Elsevier, 2017) Partyka, Kristen L.; Wu, Howard H.; Department of Pathology and Laboratory Medicine, School of MedicineIntroduction Widespread use of ultrasound allows for detection of smaller thyroid nodules and preoperative evaluation with fine-needle aspiration (FNA). Both incidental and non-incidental microcarcinoma can be found, leading to uncertainty with clinical management. Materials and methods A retrospective analysis of thyroid FNAs performed at our institution was conducted for the 5-year period from 2010 to 2014. Aspirates were categorized using the Bethesda System for Reporting Thyroid Cytopathology. Cytologic diagnoses were then correlated with final histopathology. Among samples with malignancy on surgical resection, nodules were stratified by size. Results A total of 2531 thyroid FNAs were identified; 587 samples had histologic correlation, and 259 malignancies were reported. They were separated into nodules >1 cm (n = 144, 56%) and ≤1 cm (n = 115, 44%). Microcarcinoma was further subdivided into incidental (size ≤0.5 cm, n = 55, 48%) and non-incidental (size >0.5 cm and ≤1 cm, n = 60, 52%). The preoperative cytologic diagnoses for incidental microcarcinoma were: benign (B, n = 11, 20%), follicular lesion of undetermined significance (FLUS, n = 15, 27%), follicular neoplasm (FN, n = 11, 20%), suspicious for malignancy (SM, n = 7, 13%), malignant (M, n = 8, 15%), and nondiagnostic (ND, n = 3, 5%). The FNA categories for non-incidental microcarcinoma were: B (n = 13, 22%), FLUS (n = 3, 5%), FN (n = 3, 5%), SM (n = 10, 17%), M (n = 29, 48%), and ND (n = 2, 3%). Conclusions Incidental microcarcinoma is not an uncommon entity, making up 21% (55 of 259) of malignant nodules on thyroidectomy. Indeterminate diagnoses (FLUS + FN + SM) accounted for the majority (60%) of preoperative FNAs for incidental microcarcinoma, compared with 27% for those of non-incidental microcarcinoma (P < 0.05, χ2 test).Item Florid splenic γ/δ T-cell proliferation in patients with splenomegaly and cytopenias: a “high stakes” diagnostic challenge(Elsevier, 2017-08) Zhang, Shanxiang; Bayerl, Michael G.; Department of Pathology and Laboratory Medicine, School of MedicineSplenic γ/δ T-cell proliferation is rare, and correct diagnosis is critical for adequate clinical management. Two splenectomy cases from patients with splenomegaly and cytopenias were studied by morphological evaluation, extensive immunophenotyping, FISH and molecular studies. The clinicopathologic findings were compared with splenic T γ/δ neoplasia, notably hepatosplenic T-cell lymphoma (HSTL) and T-cell large granular lymphocytic leukemia (TLGL) of the variety T γ/δ. The enlarged spleens showed expanded red pulp with markedly increased γ/δ T cells, which share significant to complete overlapping morphology and immunophenotype with the neoplastic γ/δ T cells in HSTL and γ/δ TLGL. However, they were polyclonal by molecular study and showed no evidence of isochromosome 7q. Splenectomy alone led to long-term clinical remission in both patients. Two florid reactive splenic γ/δ T-cell proliferations mimicking γ/δ T-cell neoplasia were reported for the first time in English literature. Recognition of this exceedingly rare phenomenon is critical in prevention of misdiagnosis with potentially catastrophic consequences.Item Golgi-associated LC3 lipidation requires V-ATPase in noncanonical autophagy(Nature Publishing Group, 2016-08-11) Gao, Ying; Liu, Yajun; Hong, Liang; Yang, Zuolong; Cai, Xinran; Chen, Xiaoyun; Fu, Yuanyuan; Lin, Yujie; Wen, Weijie; Li, Sitong; Liu, Xingguo; Huang, Heqing; Vogt, Andreas; Liu, Peiqing; Yin, Xiao-Ming; Li, Min; Department of Pathology and Laboratory Medicine, School of MedicineAutophagy is an evolutionarily conserved catabolic process by which cells degrade intracellular proteins and organelles in the lysosomes. Canonical autophagy requires all autophagy proteins (ATGs), whereas noncanonical autophagy is activated by diverse agents in which some of the essential autophagy proteins are dispensable. How noncanonical autophagy is induced and/or inhibited is still largely unclear. In this study, we demonstrated that AMDE-1, a recently identified chemical that can induce canonical autophagy, was able to elicit noncanonical autophagy that is independent of the ULK1 (unc-51-like kinase 1) complex and the Beclin1 complex. AMDE-1-induced noncanonical autophagy could be specifically suppressed by various V-ATPase (vacuolar-type H(+)-ATPase) inhibitors, but not by disturbance of the lysosome function or the intracellular ion redistribution. Similar findings were applicable to a diverse group of stimuli that can induce noncanonical autophagy in a FIP200-independent manner. AMDE-1-induced LC3 lipidation was colocalized with the Golgi complex, and was inhibited by the disturbance of Golgi complex. The integrity of the Golgi complex was also required for multiple other agents to stimulate noncanonical LC3 lipidation. These results suggest that the Golgi complex may serve as a membrane platform for noncanonical autophagy where V-ATPase is a key player. V-ATPase inhibitors could be useful tools for studying noncanonical autophagy.Item Immunophenotypic Comparison of Testicular Sclerosing Sertoli Cell Tumors and Sertoli Cell Tumors Not Otherwise Specified(Elsevier, 2017-09) Mesa, Hector; Zhang, Chen; Manivel, Juan C.; Ulbright, Thomas M.; Department of Pathology and Laboratory Medicine, School of MedicineTesticular Sertoli cell tumors (SCTs) are rare, and most fall into the category of SCT–not otherwise specified (SCT-NOS). Only a few additional types of SCT are recognized. Sclerosing SCT (S-SCT), originally described in 1991, comprises a small fraction of SCTs and was considered a specific entity until the 2016 revision of the World Health Organization classification of non–germ cell tumors, where it was classified as a morphologic variant of SCT-NOS. In a recent study, differences in expression of PAX2/PAX8, inhibin, androgen receptor, and S100 protein between SCT-NOS and S-SCT were noted in a small number of cases. In this interinstitutional study, we compared the expression of these markers and β-catenin in 11 cases each of SCT-NOS and S-SCT to determine if differences exist that could justify keeping a separate classification of these neoplasms. PAX2/PAX8 cocktail was the only marker that was significantly overexpressed in S-SCT. Expression of androgen receptors was strong in S-SCT and variable in SCT-NOS but did not reach statistical significance. Expression of β-catenin was common in both, whereas inhibin was infrequent. The available material was insufficient for a conclusive evaluation of S100 protein expression. Overall, our results support the inclusion of S-SCT as a morphologic variant of SCT-NOS. Expression of PAX2/PAX8 in S-SCT may reflect an overactive epithelial-to-mesenchymal transition as has been shown in experimental models of acute and chronic seminiferous tubular injury and might be related to the process generating the stroma in these tumors.Item Morphologic Spectrum of Renal Cell Carcinoma, Unclassified: An Analysis of 136 Cases(Wiley, 2017) Perrino, Carmen M.; Grignon, David J.; Williamson, Sean R.; Idrees, Muhammad T.; Eble, John N.; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of MedicineAims Renal cell carcinoma, unclassified (RCCU) is a category that includes a morphologically and biologically heterogeneous group of tumors that are unable to be diagnosed as other well-defined entities. We aim to describe the morphologic findings of tumors within this category and to determine the most frequent morphologic features leading to classification difficulty. Methods and results One hundred and thirty-six cases of RCCU were examined. Patients ranged in age from 23 to 87 years. Seventy-seven patients were men and 59 were women. International Society of Urological Pathology (ISUP) grade was most commonly 3 (n=66), followed by 2 (n=42) and 4 (n=28). Tumor size ranged from 0.6 cm to 24.9 cm. The AJCC pathologic T categories included pT1a (n=50), pT1b (n=14), pT2a (n=7), pT2b (n=4), pT3a (n=50), and pT4 (n=9). Forty-four cases included lymph node(s), of which 41% (n=18) had metastases. Tumors were assessed for a variety of histologic features and assigned to the following morphologic groups: predominantly oncocytoma/chromophobe RCC-like; clear cell RCC-like; papillary RCC-like; collecting duct-like; and pure sarcomatoid differentiation. The majority of the oncocytoma/chromophobe and clear cell RCC-like phenotypes were low stage (pT1 or pT2). The papillary RCC-like, collecting duct-like, and pure sarcomatoid phenotypes were mostly high stage (pT3 or pT4). Conclusions RCCU is a term that encompasses tumors with a variety of morphologic features and a wide biologic spectrum. The most common source of diagnostic difficulty was tumors composed of predominantly eosinophilic cells.Item Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction(Informa UK (Taylor & Francis), 2016-06-02) Livingston, Man J.; Ding, Han-Fei; Huang, Shuang; Hill, Joseph A.; Yin, Xiao-Ming; Dong, Zheng; Department of Pathology and Laboratory Medicine, School of MedicineRenal fibrosis is the final, common pathway of end-stage renal disease. Whether and how autophagy contributes to renal fibrosis remains unclear. Here we first detected persistent autophagy in kidney proximal tubules in the renal fibrosis model of unilateral ureteral obstruction (UUO) in mice. UUO-associated fibrosis was suppressed by pharmacological inhibitors of autophagy and also by kidney proximal tubule-specific knockout of autophagy-related 7 (PT-Atg7 KO). Consistently, proliferation and activation of fibroblasts, as indicated by the expression of ACTA2/α-smooth muscle actin and VIM (vimentin), was inhibited in PT-Atg7 KO mice, so was the accumulation of extracellular matrix components including FN1 (fibronectin 1) and collagen fibrils. Tubular atrophy, apoptosis, nephron loss, and interstitial macrophage infiltration were all inhibited in these mice. Moreover, these mice showed a specific suppression of the expression of a profibrotic factor FGF2 (fibroblast growth factor 2). In vitro, TGFB1 (transforming growth factor β 1) induced autophagy, apoptosis, and FN1 accumulation in primary proximal tubular cells. Inhibition of autophagy suppressed FN1 accumulation and apoptosis, while enhancement of autophagy increased TGFB1-induced-cell death. These results suggest that persistent activation of autophagy in kidney proximal tubules promotes renal interstitial fibrosis during UUO. The profibrotic function of autophagy is related to the regulation on tubular cell death, interstitial inflammation, and the production of profibrotic factors.