Solid papillary renal cell carcinoma: clinicopathologic,morphologic, and immunohistochemical analysis of 10 cases and review of the literature

Solid papillary renal cell carcinoma is rarely reported in the literature, and its tumor characteristics are not entirely compatible with the concept of 2 histological subtypes of papillary renal cell carcinoma (PRCC). Tumor is composed mostly of small compressed tubules and short abortive papillae giving solid appearance of monomorphic epithelial cells with scanty cytoplasm and small nuclei, sometimes mimicking spindle cells, without or with sparse true papillae. It shows immunohistochemical (+ CK7, + EMA, + AMACR) and genetic hallmarks (polysomy/trisomy 7/17, loss of Y) of conventional PRCC. About 53 cases have been described in the literature, with male predominance and age ranging from 17 to 82 years. By available follow-up data, solid PRCC has a favorable clinical course. We describe 10 cases compatible with the diagnosis of solid PRCC. All patients were males age range was from 34 to 70 years, and all but one were pT1 according to TNM 2009. On follow-up, 9 patients were without evidence of disease, and 1 had recurrent tumor. Size of the tumor ranged from 1.4 to 5.5 cm (mean, 3.32 cm). Tumors were well-circumscribed whitish to yellow masses with granular surface. Although solid architecture was a prominent morphologic feature, detailed analysis revealed that the tumors were composed of compressed short abortive papillae and compressed tubules admixed with true solid areas. Well-formed papillae were exceptionally present. All 10 cases were strongly and diffusely positive for CK7 and negative for WT-1. In conclusion, solid PRCC is a rare tumor with an incidence of less than 1% of all renal tumors. In majority of the cases, tumors were composed of tightly compressed tubular structures and short abortive papillae that render a solid morphologic appearance. Immunohistochemical and molecular features do not differ from conventional PRCC. Metanephric adenoma; epithelioid nephroblastoma; and, rarely, mucinous tubular and spindle cell carcinoma and oncocytic variant of PRCC should be considered in the differential diagnosis.     

Papillary renal cell carcinoma with oncocytic cells and nonoverlapping low grade nuclei: expanding the morphologic spectrum with emphasis on clinicopathologic, immunohistochemical and molecular features

Papillary renal cell carcinoma (PRCC), a morphologically and genetically distinct subtype of RCC, is morphologically separated into 2 subtypes, type 1 and 2, for prognostic purposes. Type 1 PRCC (single layer of small cells, scant pale cytoplasm) is more common and has a favorable prognosis compared with type 2 (pseudostratified high-grade nuclei, abundant eosinophilic/oncocytic cytoplasm). We report the clinicopathologic, immunohistochemical, and molecular data of 7 adult papillary tumors with morphological features distinct from type 1 or 2 PRCC. All tumors demonstrated predominant papillary architecture, lined by cells with oncocytic cytoplasm, and nonoverlapping low Fuhrman grade nuclei (1 or 2). Foamy macrophages were noted in 2 of 7 tumors. No case demonstrated necrosis or psammoma bodies. Most tumors (6/7) were small (mean size, 2.0 cm; range, 0.8-5.7 cm) and limited to the kidney. No tumor recurrence or metastasis was identified (median follow-up, 22 months). All tumors demonstrated trisomy for 7 and 17 by fluorescence in situ hybridization analysis and uniform CK 7, CD10, and alpha-methylacyl-coenzyme A racemase expression, characteristic of PRCC. These results suggest that these tumors are distinct from type 1 (owing to oncocytic cells) and type 2 (owing to low-grade nonstratified nuclei, low stage, and good outcome). Awareness of this favorable spectrum of PRCC is important to avoid its potential misinterpretation as an aggressive type 2 PRCC (owing to oncocytic cells) or rarely as an oncocytoma (owing to oncocytic cells and low-grade nuclei). Morphologic spectrum of these PRCCs emphasizes that the future prognostic model of PRCC may need to be based primarily on the nuclear characteristics, irrespective of the cytoplasmic features.     

The Gleason pattern 4 in radical prostatectomy specimens in current practice - Quantification,morphology and concordance with biopsy

PurposeThe upgrading of a prostate acinar adenocarcinoma grade group 1 (GG1) between needle biopsy and prostatectomy is common. The extent of high-grade tumor and cribriform morphology are currently suggested as prognostic factors.MethodsWe reviewed 159 prostatectomy specimens from a private laboratory and an academic/public institution in Salvador, Bahia.ResultsTumors signed as GG1 at biopsy were upgraded in 59% of all cases. These tumors showed a low frequency of non-focal extraprostatic extension (one case, 3%), extensive positive surgical margins (two cases, 6%) and seminal vesicle invasion (one case, 3%). Among GG2 and GG3 tumors at prostatectomy, the percentage of Gleason pattern 4 (Gp4) involving the gland at ≤ 1%, 2–5% and > 5% was associated with extensive extraprostatic extension (9%, 8% and 42%, respectively) and seminal vesicle invasion (1%, 10% and 31%, respectively). The volume of Gp4 of ≤ 1 ml, > 1 to 2 ml and > 2 ml was associated with extensive extraprostatic extension (8%, 26% and 38%, respectively), seminal vesicle invasion (2%, 21% and 33%, respectively) and non-focal positive surgical margins (12%, 26% and 29%, respectively). Some GG2 tumors (~ 20%) indeed showed at least one measurement of Gp4 higher than one quarter of GG3 carcinomas. Cribriform morphology showed no significant associations for other adverse pathologic prognostic factors.ConclusionUpgrading from GG1 to GG2 is associated with a very low frequency of morphologic features associated with poor prognosis. Routine quantification of Gp4 is feasible in radical prostatectomy products and seems to better stratify tumors regarding the association with other morphologic parameters of prognostic importance.     

Papillary renal cell carcinoma with prominent spindle cell stroma - tumor mimicking mixed epithelial and stromal tumor of the kidney: Clinicopathologic,morphologic, immunohistochemical and molecular genetic analysis of 6 cases

Papillary renal cell carcinoma (PRCC) is currently a well-studied type of RCC. In addition to PRCC type 1, there are a number of other subtypes and variants of PRCCs which have been reported. We describe a series of 6 PRCCs with papillary, micropapillary and/or tubulopapillary architecture and prominent spindle cell stroma, resembling stroma in mixed epithelial and stromal tumor of the kidney (MESTK) or sarcomatoid RCC.Clinicopathologic, morphologic, immunohistochemical and molecular features were analyzed.All patients were males with an age range of 44–98 years (mean 65.3, median 65.5 years). Tumor size ranged from 2.4–11.4 cm (mean 5.8, median 4.5 cm). Follow-up data were available for 4 patients, ranging from 3 to 96 months (mean 42.75, median 36 months). Epithelial cells were mostly cylindrical with eosinophilic cytoplasm, showing nuclear grade 2 and 3 (ISUP/WHO).In all cases, loose to compact prominent stroma composed of spindle cells, without malignant mesenchymal heterologous elements was detected. No atypical mitoses were found, while typical mitoses were rare in both epithelial and stromal components.Epithelial cells were positive for CK7, AMACR, and vimentin in all cases, while negative for TFE3, HMB45, desmin, CD34, and actin. The stroma was positive for vimentin, actin and focally for CD34, while negative for CK7, AMACR, TFE3, HMB45, and desmin. Estrogen and progesterone receptors were completely negative. FH and SDHB expression was retained in all analyzable cases. Proliferative index was barely detectable in stromal component and low in epithelial component, ranging 0 to 5% positive stained cells/high power field.Copy number variation was variable with no distinct pattern. No mutations in CDKN2A, BAP1, MET were detected.PRCC with MESTK-like features is a distinct variant of PRCC mimicking MESTK. Our findings add to the body of literature on ever expanding variants of PRCCs. Both epithelial and stromal components lacked true Müllerian features, which was also proven by immunohistochemistry.     

Whorling cellular perineurioma: A previously undescribed variant closely mimicking monophasic fibrous synovial sarcoma

The authors present a distinctive perineurioma (PN) variant which morphologically strongly resembles monophasic fibrous synovial sarcoma (MSS). The patients were 3 males and 1 female. The age ranged from 15 to 61 years (mean: 44 years). Locations included the sole, lower jaw, palm and foot. The tumor size ranged from 1.3 cm to 2.5 cm in the largest dimension (mean 1.8 cm). Morphologically, all tumors had an identical, monotonous appearance. The perineurial cells were closely packed and created a confluent cellular whorls and/or sheets in a scarce stroma, with only focally discernible long, slender cytoplasmic processes typical for perineurial differentiation. The nuclei were rounded or slightly elongated to tapered, without nuclear atypia. Mitoses were rare to completely absent. Atypical mitoses, hemorrhage, necrosis or calcifications were not present. The proliferative index (Ki-67) was 1–3%. All analyzed tumors were positive for EMA, Claudin-1, GLUT-1 and negative with S100 protein, CD34, OSCAR, CK7 and TLE-1. Two cases were tested by fluorescence in situ hybridization and neither showed alterations of the SYT gene. One case studied by electron microscopy showed characteristic features of perineurial differentiation. Follow-up was available for two patients both of which showed no evidence of disease at 8 years and 6 months, respectively. Based on their bland morphology, perineurial features and presumably benign clinical outcome we propose the term “whorling cellular perineurioma” for these tumors, which may represent an extremely cellular variant of sclerosing PN. Awareness of this PN subtype and its distinction from MSS is of utmost clinical significance.     

CD34low and SMAhigh represent stromal signature in uterine cervical cancer and are markers for peritumoral stromal remodeling

Peritumoral desmoplastic stromal reaction (DSR) with myofibroblastic phenotype may be of prognostic impact in uterine cervical carcinoma. The present study evaluates the immunostaining (CD34 and smooth muscle actin; SMA) of 97 squamous cell cancers. Staining was scored as low/negative (< 5% stroma positive), moderate (patchy/focal expression, 5%-50%), or high (diffuse expression throughout peritumoral stroma, > 50%) and DSR as negative/weak and moderate/strong. The staining results were correlated to patient survival. Of the cases, 78.3% showed a decreased of CD34 (< 5% stromal positivity) and 71.9% an increased SMA staining with more than 50% SMA positive stromal cells. Tumors representing moderate/strong DSR showed a significant decreased CD34 (P = .001) and an increased but not statistically significant SMA staining (P = 0.345). Cases with low CD34 and high SMA staining showed reduced 5-year overall survival when compared to cases with high CD34 and low SMA positivity (59.9 vs 81.0%; P = 0.025 and 64.6 vs 81.1%; P = 0.243). Peritumoral stromal response in cervical carcinoma is immunohistochemically characterized by CD34^low/SMA^high and associated reduced overall survival.     

On the association between glioma,wireless phones,heredity and ionising radiation

We performed two case–control studies on brain tumours diagnosed during 1 January 1997 to 30 June 2000 and 1 July 2000 to 31 December 2003, respectively. Living cases and controls aged 20–80 years were included. An additional study was performed on deceased cases with a malignant brain tumour using deceased controls. Pooled results for glioma yielded for ipsilateral use of mobile phone odds ratio (OR) = 2.9, 95% confidence interval (CI) = 1.8–4.7 in the >10 years latency group. The corresponding result for cordless phone was OR = 3.8, 95% CI = 1.8–8.1. OR increased statistically significant for cumulative use of wireless phones per 100 h and per year of latency. For high-grade glioma ipsilateral use of mobile phone gave OR = 3.9, 95% CI = 2.3–6.6 and cordless phone OR = 5.5, 95% CI = 2.3–13 in the >10 years latency group. Heredity for brain tumour gave OR = 3.4, 95% CI = 2.1–5.5 for glioma. There was no interaction with use of wireless phones. X-ray investigation of the head gave overall OR = 1.3, 95% CI = 1.1–1.7 for glioma without interaction with use of wireless phones or heredity. In conclusion use of mobile and cordless phone increased the risk for glioma with highest OR for ipsilateral use, latency >10 years and third tertile of cumulative use in hours. In total, the risk was highest in the age group <20 years for first use of a wireless phone.     

Clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 expression in Tunisian gastric adenocarcinomas

Gastric carcinoma (GC) is a highly aggressive malignancy with poor prognosis. It is widely accepted that malignancy results from abnormal cell growth due to dysregulation of the balance between cell proliferation and apoptosis. Our study aimed to investigate the clinicopathological and prognostic significance of p53, Ki-67, and Bcl-2 in Tunisian GC patients by immunohistochemistry. It was observed that the older patients showed p53 overexpression compared with the younger patients (p < 0.05). There was higher p53 expression in the intestinal-type compared with the diffuse-type (p < 0.05), and in well/moderate differentiated than in poor differentiated tumors. The expression of Ki-67 was positively associated with tumor size and venous invasion (p < 0.05). Bcl2 expression occurred in male patients and correlated with depth of invasion (p = 0.02). A Kaplan–Meier analysis indicated an inverse correlation between p53 and Ki-67 expression and the overall survival. Multivariate analysis revealed that the tumor site, Ki-67 and p53 expression were independent prognostic factors for gastric carcinomas (p < 0.05). Finally, combined expression of p53, Ki-67 and Bcl-2 showed that the group of patients with tumors p53+/Ki-67+/Bcl2− had aggressive behavior and poor prognosis (p log rank = 0.000). In summary, our data indicated that the expression of p53, Ki-67, and Bcl-2 may provide useful information for identifying patients with aggressive behavior and poor prognosis of GC.     

Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients

Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P = 0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are < 40 years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value = 0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value = 0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value = 0.0001). No significant associations between cyclin D1 immunohistochemical staining and grade, recurrence and alive status were observed. Significant different survival distributions were observed (P-value = 0.011) and poor survival behavior was correlated with negative cyclin D1 immunohistochemical staining. In conclusion, greater frequency of cyclin D1 expression was revealed in normal endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients.     

Cutaneous hidradenoma: a study of 21 neoplasms revealing neither correlation between the cellular composition and CRTC1-MAML2 fusions nor presence of CRTC3-MAML2 fusions

Twenty-one hidradenomas from 20 patients (13 female, 7 male) ranging in age from 18 to 87 years (mean, 57.75 years; median, 60 years) were studied for CRTC1-MAML2 and CRTC3-MAML2 fusions to find out whether there is a correlation between the particular cell type (polyhedral eosinophilic, clear, mucinous, epidermoid, and oncocytic) and presence the above alterations. CRTC1-MAML2 fusions were detected in 10 of the 21 neoplasms (47.6%). Fluorescence in situ hybridization for MAML2 break apart was analyzable in 13 specimens and in all these specimens was positive, including 4 tumors with no demonstrable CRTC1-MAML2 fusion. In none of the cases was a CRTC3-MAML2 fusion detected. No obvious correlation between the cellular composition and presence of t(11,19) translocation was found.     

Cystic and necrotic papillary renal cell carcinoma: prognosis,morphology, immunohistochemical,and molecular-genetic profile of 10 cases

Conflicting data have been published on the prognostic significance of tumor necrosis in papillary renal cell carcinoma (PRCC). Although the presence of necrosis is generally considered an adverse prognostic feature in PRCC, we report a cohort of 10 morphologically distinct cystic and extensively necrotic PRCC with favorable biological behavior. Ten cases of type 1 PRCC with a uniform morphologic pattern were selected from the 19 500 renal tumors, of which 1311 were PRCCs in our registry. We focused on precise morphologic diagnosis supported by immunohistochemical and molecular-genetic analysis. Patients included 8 men and 2 women with an age range of 32-85 years (mean, 62.6 years). Tumor size ranged from 6 to 14 cm (mean, 9.4 cm). Follow-up data were available in 7 patients, ranging from 0.5 to 14 years (mean, 4 years). All tumors were spherical, cystic, and circumscribed by a thick fibrous capsule, filled with hemorrhagic/necrotic contents. Limited viable neoplastic tissue was present only as a thin rim in the inner surface of the cyst wall, consistent with type 1 PRCC. All cases were positive for AMACR, OSCAR, CAM 5.2, HIF-2, and vimentin. Chromosome 7 and 17 polysomy was found in 5 of 9 analyzable cases, 2 cases demonstrated chromosome 7 and 17 disomy, and 1 case showed only chromosome 17 polysomy. Loss of chromosome Y was found in 5 cases, including 1 case with disomic chromosomes 7 and 17. No VHL gene abnormalities were found. Papillary renal cell carcinoma type 1 can present as a large hemorrhagic/necrotic unicystic lesion with a thick fibroleiomyomatous capsule. Most cases showed a chromosomal numerical aberration pattern characteristic of PRCC. All tumors followed a nonaggressive clinical course. Large liquefactive necrosis should not necessarily be considered an adverse prognostic feature, particularly in a subset of type 1 PRCC with unilocular cysts filled with necrotic/hemorrhagic material.     

Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change

Several studies have documented phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy [NACT], but many of these studies are limited by the fact that they did not account for the baseline rate of expected phenotypic change between biopsies and resections in the absence of NACT. Herein, we assess whether the NACT-associated rate of phenotypic change is significantly different than would be expected in a control population of patients that did not receive NACT. From a pathologic database, we documented the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) phenotypes of consecutive invasive breast carcinomas (n = 826), as well as the subset in which at least one of these tests was assessed in both the biopsy and resection (n = 340). We then compared the rates of phenotypic change in the patients that did (n = 65) and did not (n = 275) receive NACT. Respectively, 49.2% and 36% of the NACT and non-NACT groups showed a biopsy-to-resection change in status for at least one biomarker (p = 0.0005). The NACT and non-NACT groups showed the following respective rates of a biopsy-to-resection change in phenotype: ER (9.2% vs 2.5%, p = 0.02); PR (30.7% vs 8%, p = 0.000006); Her2/neu-IHC (25% vs 22.3%, p = 0.7), Her2/neu-FISH (7% vs 3%, p = 0.6). The direction of change in the NACT group was positive in the biopsy to negative in the resection in > 70% of cases for all markers. For ER and PR, there was no statistically significant difference between cases that showed a biopsy-to-excision change in phenotype and those that were more phenotypically stable regarding a wide array of clinicopathologic variables. The average percentage of ER/PR-immunoreactive tumor cells in the pre-NACT biopsies was significantly lower in the phenotypically altered cases as compared to the phenotypically stable cases. Our findings confirm that phenotypic alterations in breast cancer occur after NACT, and that these changes are more pronounced for hormone receptors (especially PR); Significant NACT-associated alterations were not apparent for HER2/neu. A distinct pathologic profile for cases displaying a phenotypic change within the NACT group was not demonstrable. The pre-NACT levels of ER and PR may affect the likelihood of a phenotypic change. These results highlight the need for repeat testing in residual tumors after NACT.     

CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer

Tumor associated macrophages (TAM) support tumor growth and metastasis in several animal models of breast cancer, and TAM amount is predictive for efficient tumor growth and metastatic spread via blood circulation. However, limited information is available about intratumoral TAM heterogeneity and functional role of TAM subpopulations in tumor progression. The aim of our study was to examine correlation of TAM presence in various morphological segments of human breast cancer with clinical parameters. Thirty six female patients with nonspecific invasive breast cancer T1-4N0-3M0 were included in the study. Morphological examination was performed using Carl Zeiss Axio Lab.A1 and MiraxMidiZeiss. Immunohistochemical and immunofluorescence/confocal microcopy analysis was used to detect CD68 and stabilin-1 in 5 different tumor segments: (1) areas with soft fibrous stroma; (2) areas with coarse fibrous stroma; (3) areas of maximum stromal-and-parenchymal relationship; (4) parenchymal elements; (5) gaps of ductal tumor structures. The highest expression of CD68 was in areas with soft fibrous stroma or areas of maximum stromal-and-parenchymal relationship (79%). The lowest expression of CD68 was in areas with coarse fiber stroma (23%). Inverse correlation of tumor size and expression of CD68 in gaps of tubular tumor structures was found (R = −0.67; p = 0.02). In case of the lymph node metastases the average score of CD68 expression in ductal gaps tumor structures was lower (1.4 ± 0.5) compared to negative lymph nodes case (3.1 ± 1.0; F = 10.9; p = 0.007). Confocal microscopy identified 3 phenotypes of TAM: CD68⁺/stabilin-1⁻; CD68⁺/stabilin-1⁺ (over 50%); and CD68⁻/stabilin-1⁺. However, expression of stabilin-1 did not correlate with lymph node metastasis. We concluded, that increased amount of CD68+TAM in gaps of ductal tumor structures is protective against metastatic spread in regional lymph nodes.     

Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. A clinicopathologic,immunophenotypic and molecular analysis

BackgroundDespite extensive immunohistochemical (IHC) and molecular studies combined with morphologic findings, a group of round/ovoid cell tumors histologically similar to Ewing sarcomas (ES) but lacking EWSR1-rearrangements may remain unclassifiable.DesignWe retrospectively analyzed 41 Ewing-like tumors (formalin-fixed, paraffin-embedded) previously determined as negative or non-informative for EWSR1-rearrangements by FISH and/or RT-PCR. A new histopathology revision and additional IHC and molecular analyses were carried out in order to investigate whether additional IHC and/or molecular testing in combination with the morphological findings may help in reaching a definitive diagnosis.ResultsAlmost all the tumors (n = 40) involved soft tissue and/or bone and half the patients died of disease. In the archival cases all diagnoses were Ewing sarcoma (ES), Ewing-like sarcoma (ELS), myoepithelial tumor and undifferentiated sarcoma (US). In the new review all the tumors were re-classified as, ES (n = 16), Ewing-like tumor with EWSR1 rearrangement and amplification and possible EWSR1-NFATC2 gene fusion (n = 1), CIC-rearranged sarcomas or undifferentiated sarcoma, most consistent with CIC-rearranged sarcoma (n = 7), sarcoma with BCOR-alteration or undifferentiated sarcoma, consistent with BCOR-associated sarcoma (n = 3), neuroblastoma (n = 2), unclassifiable neoplasm with neuroblastic differentiation (n = 1), malignant rhabdoid tumor (n = 2), lymphoblastic lymphoma (n = 1), clear cell sarcoma of the gastrointestinal tract (n = 1), small cell carcinoma (n = 1), sclerosing rhabdomyosarcoma (n = 1), desmoplastic small round cell tumor (n = 1), malignant peripheral sheath nerve tumor (n = 1), poorly-differentiated synovial sarcoma (n = 1), Possible gastrointestinal stromal tumor/GIST with predominant round cells (n = 1) and possible SMARCA4-deficient-sarcoma (n = 1). NKX2.2, ETV4 and BCOR immunoreactivity was observed in all ES, CIC-rearranged sarcomas and sarcomas with BCOR alteration, respectively. CIC-rearrangement by FISH was observed in many of the CIC-rearranged sarcomas.ConclusionOur analysis of 41 Ewing-like tumors confirms that there may be a significant pathological and IHC overlap among Ewing-like tumors, with prognostic and therapeutic impacts. Additional IHC (NKX2.2, ETV4 and BCOR) and molecular studies including FUS, CIC or BCOR analysis may support the final diagnosis when FISH or RT-PCR fail to detect EWSR1-rearrangements. Any molecular findings should always be interpreted in relation to the specific clinical and pathological context.     

Thrombus age,clinical presentation,and reperfusion grade in myocardial infarction

IntroductionAutopsy studies show that dynamic coronary thrombosis leads to infarction. We studied intracoronary thrombus age in ST-segment elevation myocardial infarction (STEMI) and its relationship with clinical presentation and epicardial reperfusion grade.Methods and resultsIntracoronary thrombectomy was performed in 131 STEMI patients within 24 h after symptom onset, and material sufficient for pathological analysis was retrieved from 81 patients. Thrombus age was classified as fresh (<1 day), lytic (1 to 5 days), or organized (>5 days). A fresh thrombus was found in 48 patients (60%), whereas the thrombus showed lytic or organized changes in 33 patients (40%). Both thrombus and plaque material were aspirated in 40% of cases. Lytic or organized thrombi were aspirated in one third of the cases early (<12 h) after symptom onset, and fresh thrombi were also aspirated in one third of STEMI of > 12 h evolution. In multivariable analysis, fresh thrombus was associated with both persistent ST-segment elevation (even after 12 h of onset) during percutaneous coronary intervention [odds ratio (OR) 4.23, 95% confidence interval (CI) 1.05–17.42, P = .042) and a previous history of ischemic heart disease (OR 4.54, 95% CI 1.41–14.64, P = .011). There were no associations between thrombus composition and epicardial reperfusion grade or the presence of the no-reflow phenomenon. Plaque components were found in all cases of distal embolization (5%).ConclusionIntracoronary thrombi aspirated in STEMI frequently show more than one stage of maturation. Fresh thrombi predominate in patients with known ischemic heart disease or persistent ST-segment elevation.SummaryIn STEMI, thromboaspiration revealed thrombi at different stages of maturation, supporting a dynamic process of rupture and repair of the atherosclerotic plaque. Fresh thrombi were present more frequently within 12 h of infarction onset but also in patients with symptoms beyond 12 h. When containing plaque material, thrombi were often associated with macroscopic distal embolization during angioplasty.     

Human papillomavirus detection in fine needle aspiration cytology of lymph node metastasis of head and neck squamous cell cancer

BackgroundCurrently, testing on HPV in oropharyngeal squamous cell carcinoma (OPSCC) is performed on histological material. However, in a certain percentage of the cases who present with lymph node metastases no primary tumor can be identified and only fine needle aspiration cytology (FNAC) is available for analysis.ObjectivesPurpose of this study was to assess HPV status on FNAC and to validate it using histological material of the same patients.Study designPatients with cervical metastasis from OPSCC or cancer of an unknown primary tumor (CUP), diagnosed between 2007 and 2012 were included. In 6 of the 47 patients, no primary tumor could be identified. HPV detection and genotyping was performed in both FNAC slides scrapings and formalin fixed paraffin embedded (FFPE) histological material from the same patients, using the HPV SPF₁₀-LiPA₂₅ assay. HPV PCR analysis on FFPE material was considered the reference standard for HPV status of each case.ResultsCompared with HPV negative cases (n = 22), significantly more HPV positive cases (n = 25) presented initially with cervical metastasis (27% vs 56% respectively; p = 0·047). The HPV PCR assay on FNAC material showed a high sensitivity (96%; 95% CI 86.6–97.4) and specificity (100%; 95% CI 85.1–96.7) using the reference standard of HPV PCR analysis on FFPE material of the same patients.ConclusionIn this study, testing on HPV in FNAC of cervical lymph node metastases of SCC is validated. It provides a valuable alternative for testing of HPV on histological material from patients with oropharyngeal squamous cell carcinoma or cancer of an unknown primary tumor.     

Furan-induced dose–response relationships for liver cytotoxicity,cell proliferation,and tumorigenicity (furan-induced liver tumorigenicity)

Rodent studies of furan are associated with liver cell necrosis, release of liver-associated enzymes, increased hepatocyte proliferation, and hepatocarcinogenesis. For carcinogens whose proposed mode of action is cytolethality, it is hypothesized that the dose–response curve for tumor development would parallel the dose–response curve for cell death with compensatory proliferation in the target organ. To prospectively test this hypothesis, female B6C3F₁ mice were exposed to furan at carcinogenic doses and lower for 3 weeks or 2 years. At 3 weeks and in the 2-year study, there were dose-dependent and significant increases in hepatic cytotoxicity at 1.0, 2.0, 4.0, and 8.0 mg furan/kg. For cell proliferation as measured by 5-bromo-2′-deoxyuridine (BrdU) labeling index (LI), there was a statistically significant trend with increasing dose levels of furan and increased LI at 8.0 mg/kg. There was an increased incidence of foci of altered hepatocytes, hepatocellular adenomas, and adenomas or carcinomas at 4.0 and 8.0 mg/kg and carcinomas at 8.0 mg/kg. The multiplicity of microscopic tumors was increased and latency was decreased in mice exposed to 8.0 mg/kg. Prevalence of hepatic nodules at necropsy was increased in mice exposed to 4.0 and 8.0 mg/kg. Data demonstrate an association among furan-induced hepatic cytotoxicity, compensatory cell replication, and liver tumor formation in mice; at high doses ?4.0 mg/kg, furan induced hepatotoxicity, compensatory cell replication and tumorigenesis in a dose-related manner, while furan did not produce tumors at cytotoxic doses of 1.0 and 2.0 mg/kg.     

HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 951 Southeast Asia Malays from Peninsular Malaysia

A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p < 0.0001), -B (p < 0.0001), -DRB1 (p < 0.0001) and -DQB1 (p < 0.01) loci. Minor deviations from HWEP were detected for HLA-C (p = 0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).     

The detection,treatment of parvovirus B19 infection induced anemia in solid organ transplants: A case series and literature review of 194 patients

BackgroundThere are no optimal diagnostic, treatment and post-infection surveillance strategies for parvovirus B19 infection in solid organ transplantation (SOT) recipients.MethodsWe conducted a retrospective review of all PVB19 infected cases confirmed by qPCR among SOT recipients at our institution over a 3-year period and reviewed the literature from 1990 to 2021.ResultsEight kidney and two heart transplant patients with refractory anemia had PVB19 infection. The viral DNA load in peripheral blood ranged from 2.62 × 10² to 8.31 × 10⁶ copies/mL. Two patients with the lowest PVB19 DNA load only reduced the use of immunosuppressants and anemia was relieved. Eight received intravenous immunoglobulin (IVIG) (ranging from 0.25 to 0.5 g/kg/day). The median time to anemia improvement (hemoglobulin > 100 g/L) was 16 days (8–70 days) after treatment. One patient had a PVB19 relapse and viral DNA load > 1.00 × 10⁸ copies/mL at diagnosis. A total of 86 studies involving 194 SOTs were screened from the literature, and the most common symptom was anemia and low reticulocyte count. PVB19 DNA was detected in all cases. Of that, 91.4% of cases received IVIG, 53.8% received IVIG and immunosuppression reduction, 6.5% of cases showed reduced immunosuppression without IVIG, and 2.1% did not receive any special treatment. The recurrence rate was 17.5%.ConclusionPVB19 infection is a cause of anemia after SOT, and treatment mainly relies on IVIG and/or immunosuppression reduction.