BCOR-CCNB3 Sarcoma with Prominent Rhabdoid Cells Mimicking Rhabdomyoblasts: Expanding the Morphologic spectrum of BCOR-CCNB3 Sarcoma.

BCOR-CCNB3 sarcoma (BCS) is a rare recently defined undifferentiated sarcoma that predominantly affects children and young adults. The diagnosis of this tumor is difficult due to the highly variable morphology and nonspecific immunophenotype. Emerging data suggest that patients with BCS show response to Ewing sarcoma-based treatment regimen, thus correct diagnosis is of clinical relevance. In this study, we report a case of BCS arising from the big toe of a 15-year-old male patient. The tumor had a prominent population of rhabdoid cells with bright eosinophilic cytoplasm mimicking rhabdomyosarcoma. The tumor cells were focally positive for desmin and myogenin, and negative for CD99. Next-generation sequencing showed the presence of BCOR-CCNB3 gene fusion. BCS with prominent rhabdoid cells has not been described before. This study further expands the morphologic spectrum of BCS.

Fine needle biopsy of malignant tumors of the liver: a retrospective study of 624 cases from a single institution experience.

BACKGROUND: Liver is one of the most common organs involved by metastatic neoplasms. In addition, a number of primary tumors can arise in the liver. Fine needle biopsy (FNB) is the most commonly used method for diagnosis of liver masses. Not much literature is available during the past 10 years about FNB of liver tumors. All large studies were performed more than 15 years ago. With the introduction of new disease entities, new tumor classification systems, and new diagnostic methods, updated documentation of FNB of liver neoplasms is much needed. METHODS: Liver FNB cases that were diagnosed as "Positive for Malignancy" between 2010 and 2018 were retrieved from the cytopathology database in our institution. Patient medical records, cytopathology and surgical pathology reports, and slides from selected cases were retrieved and reviewed. RESULTS: Over 30 different types of malignant tumors were identified in 624 malignant FNB cases, with the most common tumors being metastatic colorectal and pancreatic adenocarcinomas. Rare tumors include EBV-positive leiomyosarcoma, mesothelioma, and paraganglioma, among others. A subset of patients presented with widespread metastases involving liver with no known history. Identifying the primary sites in those cases can be challenging. We also found that in our practice, a significant number of hepatocellular carcinoma were diagnosed by FNB in recent years. CONCLUSIONS: A tremendous variety of neoplasms can occur in liver. Accurate diagnosis is essential for proper patient management. Familiarization with morphological features and judicious usage of ancillary studies are essential for accurate diagnosis.

Fetal Type Rhabdomyoma of the Soft Palate in an Adult Patient: Report of One Case and Review of the Literature.

Rhabdomyoma is a rare benign tumor with skeletal muscle differentiation. Rhabdomyoma is further classified into cardiac, adult, fetal, and genital subtypes. Out of these, fetal type rhabdomyoma (FTR) is the rarest. Only a small number of cases have been recorded in the literature. FTR typically affects male infants and young children and occurs predominantly in the head and neck region. FTR is exceedingly rare in the adult, with less than 30 cases reported. The classic FTR is composed of primitive undifferentiated spindle cells with scant eosinophilic cytoplasm embedded in a myxoid stroma. Immunohistochemically, the tumor cells are positive for desmin, muscle specific actin, and myogenin. Awareness and proper recognition of this rare entity is of considerable importance to avoid misdiagnosis of embryonal rhabdomyosarcoma. In this study, we report one case of FTR in an adult patient and reviewed the literature about the clinical and pathologic presentation of FTR in the adult.

Malignant perivascular epithelioid cell tumor of the oropharynx with strong TFE3 expression mimicking alveolar soft part sarcoma: a case report and review of the literature.

Perivascular epithelioid cell tumors (PEComas) in the head and neck region are rare, with 26 cases described in literature. These distinct mesenchymal tumors normally express both myoid and melanocytic markers. We here report an interesting and challenging case of malignant PEComa that showed transcription factor E3 (TFE3) protein expression and rearrangement, paucity of muscle and melanocytic marker expression, and morphologically mimicked alveolar soft part sarcoma. Awareness of this morphologic pitfall and recognition of TFE3 gene-rearranged PEComa, as a distinct subtype of PEComa, is essential to avoid misdiagnosis.

Hepatitis C virus seroprevalence in the general female population from 8 countries.

BACKGROUND: Hepatitis C virus (HCV) infection is a significant global health issue because it is widespread and persistent and can cause serious liver diseases. OBJECTIVES: The aim of this study is to estimate HCV prevalence in women from the general population in different geographical areas worldwide and to assess the potential role of sexual behaviour in the virus transmission. STUDY DESIGN: Each participating centre recruited a random sample of women from the general population aged from less than 20 to more than 75 years. The study included 8130 women from 8 countries with information on sociodemographic factors, reproductive and sexual behaviour, smoking habit and HPV DNA through individual interviews. A blood sample was also collected to perform serological tests. We estimated the prevalence ratios associated to HCV to evaluate the effect of sexual behaviour in viral transmission. RESULTS: Women were reactive to a minimum of two HCV antigens, including at least one non structural protein were considered as positive (33% of the samples were classified as positive, 40% as negative, and 27% as indeterminate (N=402), that were considered as not positive). The age-adjusted HCV seroprevalence varied significantly by regions (0.3% in Argentina to 21.1% in Nigeria). We found no association between HCV prevalence and age, educational level, smoking habit and any of the available variables for sexual behaviour and reproductive history. CONCLUSIONS: This large study showed heterogeneous distribution of HCV seroprevalence in female and provides evidence of the null impact of sexual behaviour in HCV transmission.

Acquired constricting and restricting lesions of the descending duodenum.

The descending duodenum is a structure with distinct pathologic processes and anatomic relationships that requires a systematic approach to the differential diagnosis. Because of its tubular shape and fixed position in the retroperitoneum, both intrinsic duodenal and juxtaduodenal diseases are capable of producing luminal narrowing and obstruction. Duodenal lesions may be located in the mucosa or submucosa. Extraduodenal lesions may originate in adjacent structures--such as the pancreas, liver, gallbladder, colon, and lymph nodes--or from other retroperitoneal structures. Causes of duodenal obstruction include intraluminal masses, such as bezoars; duodenal inflammation, such as as peptic ulcers and Crohn disease; hematomas; and benign or malignant mucosal and intramural tumors. Pancreatic inflammation; tumors; and extrinsic compression caused by gallbladder processes, hepatic masses, retroperitoneal fluid collections, and tumors, including lymphoma, may produce duodenal obstruction. Abdominal radiography, barium studies, multidetector computed tomography, magnetic resonance imaging, and positron emission tomography may be used to depict and characterize duodenal strictures. Integration of imaging, clinical, laboratory, and endoscopic findings plays a major role in establishing a diagnosis of obstructive duodenal strictures.

The most characteristic lesions and radiologic signs of Crohn disease of the small bowel: air enteroclysis, MDCT, endoscopy, and pathology.

This pictorial essay describes the most characteristic lesions and radiologic signs of Crohn disease of the small bowel: nodular lymphoid hyperplasia, abnormal mucosal folds, villous pattern, aphthous ulcerations, linear ulcerations, cobblestone pattern, string sign, target sign, comb sign, creeping fat, sinus tracts, fistulas, and abscesses. Each description includes the definition, a correlation with the pathologic findings, an explanation of the possible physiopathologic mechanism, sample radiologic images with air enteroclysis or MDCT, the correspondence with the endoscopic findings when possible, and a list of differential diagnoses.

The value of duplicate slides on atypical squamous cells, cannot exclude high-grade intraepithelial lesion.

Atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) category was added to the 2001 Bethesda System. ASC-H accounts for a small percentage (0.2-0.6%) of abnormal Pap smears and includes heterogenous group of lesions. There are more high-grade cervical lesions (30-50%) in ASC-H than ASC-US (10-15%). An accurate Pap diagnosis is crucial for appropriate patient follow-up and treatment. A total of 43 consecutive ASC-H cases were collected from October 2007 to March 2008, and all duplicate and the original slides were reviewed blindly at the end of the study. On review of the duplicate Pap slides, 18 cases had diagnostic SIL cells (15 HSIL, 2 LSIL with ASC-H, and 1 LSIL). The duplicate slides could have potentially changed 18 (41.9%) ASC-H diagnoses to a more definitive SIL diagnosis. On review of the original Pap slides, 8 of these 18 cases also had HSIL cells. Twenty-one follow-up cervical biopsies (21/43, 48.8%) showed 12 CIN 2/3, 4 CIN 1, 1 VAIN 1, 2 cervical polyps, 1 negative for dysplasia, and 1 insufficient for diagnosis. The CIN 2/3 rate was 57.1% (12/21) based on the original ASC-H Pap diagnosis. The CIN 2/3 rates were 80% (8/10) with SIL cells on duplicate slides and 36.4% (4/11) without SIL cases on duplicate slides. Our study suggested that duplicate slides were very useful for further classification of ASC-H, but other ancillary tests might be necessary for some cases. We propose a systematic approach using combined duplicate slides and reflex HPV testing to further classify ASC-H.

The diagnostic value of cell block as an adjunct to liquid-based cytology of bronchial washing specimens in the diagnosis and subclassification of pulmonary neoplasms.

BACKGROUND: To the authors' knowledge, the diagnostic value of cell block (CB) as an adjunct to ThinPrep liquid-based cytology (LBC) of bronchial washing specimens in the detection and subclassification of pulmonary neoplasms has not been well evaluated. The objective of the current study was to evaluate the diagnostic utility of CB in this setting. METHODS: A total of 74 bronchial washing specimens and concurrently prepared CBs with a diagnosis of malignant or suspicious/atypical obtained from bronchoscopy procedures performed during 2009 were reviewed along with 28 randomly selected negative cases. LBC and CBs were reviewed independently. Deeper levels and ancillary studies were performed on CBs for specific tumor classification if needed. LBC and CB diagnoses were correlated with final histology and/or bronchial brushings. RESULTS: Use of CBs increased the number of positive diagnoses from 18 (LBC only) to 30 (combined LBC and CB) and 36 (combined LBC and CB with ancillary studies), with increased diagnostic yields of 67% and 100%, respectively. CB without ancillary techniques detected 22 malignancies whereas LBC detected 18 malignancies and CB with ancillary techniques detected 29 malignancies. A specific tumor diagnosis was possible in 22 of 29 (76%) malignancies detected by CB. Bronchial brushings and histology confirmed malignancy in 91% and 92% of cases, respectively. CONCLUSIONS: CB combined with LBC was found to improve the rate of detection of malignancy over LBC alone, especially in cases with suspicious or atypical LBC diagnoses. Increased diagnostic yield is observed when CB is used with or without ancillary studies, but the yield is higher with CB using ancillary studies. CB serves as yet another available source of diagnostic material for immunohistochemical and molecular studies.

Is p16 immunohistochemistry a more cost-effective method for identification of human papilloma virus-associated head and neck squamous cell carcinoma?

Tobacco and alcohol use are established risk factors for head and neck squamous cell carcinoma (HNSCC). However, patients with a unique subset of human papilloma virus (HPV)-associated HNSCC have been documented to have a better survival outcome. These tumors occur more frequently in the tonsils and oropharyngeal sites, among younger patients, higher socioeconomic group, and those exposed to more sexual partners and oral sex compared with HPV-negative HNSCC. Although tobacco- and alcohol-related HNSCCs appear to be on the decline, tonsillar and oropharyngeal HPV-associated tumors seem to be on the rise, and their prevalence varies widely in published reports, ranging from 20% to 60%. Human papilloma virus detection methods in tumor tissue vary and include polymerase chain reaction, in situ hybridization (ISH) technique for HPV DNA, and E6/E7 messenger RNA, with p16 immunohistochemistry (IHC) as a surrogate marker. The sensitivity and specificity of the different methods used are likely contributory factors to this wide variation. This study compares the p16 IHC staining patterns in HNSCC and laryngeal papillomas and assesses the concordance of p16 and high-risk HPV-ISH to determine the usefulness of p16 as a first-line marker. Using an objective criterion of diffuse intense confluent staining pattern as definite positive (akin to the 3+ of HER2/neu in breast cancer) and focal scattered staining pattern as equivocal reaction requiring confirmatory HPV assay, p16 IHC expression shows good concordance with high-risk HPV-ISH and can be used as a first-line marker. We propose p16 overexpression as a suitable surrogate and screening marker, with high potential of impacting the standard of care.

Changing trends in human papillomavirus-associated head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) continues to be a significant disease with varying rates of incidence and mortality worldwide. Numerous studies have demonstrated that human papillomavirus (HPV) is etiologically linked with a subset of HNSCC, independent of tobacco and alcohol use. This subset of tumor shows increased sensitivity to radiation therapy and association with better outcomes. The study aims to determine the HPV burden and trend among patients with HNSCC in the southern region of the United States over the past 10 years. Of 142 cases from 2000 to 2004, 18 (13%) were positive for high-risk HPV. Nine of these were oropharyngeal tumors, including 4 cases from the tonsil. These constitute 38% (9/24) of all oropharyngeal tumors and 57% (4/7) of tonsillar tumors. Of 35 cases from 2009 to 2010, 14 (40%) were positive for high-risk HPV. Thirteen of these were oropharyngeal tumors, including 9 cases from the tonsil. These constitute 59% (13/23) of oropharyngeal tumors and 64% (9/14) of tonsillar tumors. When data from the 2 periods are combined, the results show that African American patients are less likely to have HPV-associated disease compared with white patients (9% vs 22%). Human papillomavirus-positive and oropharyngeal HNSCC are more likely to be nonkeratinizing (P < .0001). In conclusion, the HPV detection rate in oropharyngeal squamous cell carcinoma increased from 38% to 59% between the 2000-to-2004 and 2009-to-2010 periods.

Teenage cervical screening in a high risk American population.

BACKGROUND: The new 2009 ACOG guideline for cervical cytology screening changed the starting age to 21 years regardless of the age of onset of sexual intercourse. However, many recent studies have shown a dramatic increase in the incidence of cervical epithelial abnormalities among adolescents within the past two decades. MATERIALS AND METHODS: For this study, the reports of 156,342 cervical cytology were available of which 12,226 (7.8%) were from teenagers. A total of 192 teenagers with high grade intraepithelial lesion (HSIL) cervical cytology were identified. The ages ranged from 13 to 19 years with a mean of 17.7 years and a median of 18 years. Among them, 31.3% were pregnant, 12.0% were postpartum, and 13.5% were on oral contraceptive. Ninety-eight had prior cervical cytology. RESULTS: The teenagers had statistically significant higher detection rates of overall abnormal cervical cytology (23.6% vs. 6.6%, P = 0), with 15.4% vs. 3.2% (P = 0) of low grade intraepithelial lesion (LSIL) and 1.8% vs. 1.0% (P = 2.56 × 10(-13) ) of HSIL compared to women ≥20 years. The teenage group had the highest abnormal cytology among all age groups. The LSIL/HSIL ratio was 8.5:1 for teenagers and 3.1:1 for women ≥20 years. A total of 131 teenagers had cervical biopsies within 12 months of the HSIL cytology, with diagnoses of 39 CIN 3, 1 VAIN 3, 15 CIN 2, 62 CIN 1, and 14 had a negative histology (CIN 0). Only in 19 of these 39 women, the CIN 2/3 lesion proved to be persistent. CONCLUSION: We conclude that cytology screening of high risk teenagers is effective in detecting CIN 2/3 lesions. Moreover, treatment and careful follow-up can be realized.

Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma.

OBJECTIVE: Determine human papillomavirus (HPV) incidence in unknown primary squamous cell carcinomas (SCCa) of the head and neck and assess if HPV status influenced survival. STUDY DESIGN: Historical cohort study. SETTING: Tertiary care center. SUBJECTS: Patients with unknown primary SCCa despite a complete workup who underwent neck dissection or excisional biopsy and postoperative comprehensive ± chemoradiotherapy between 2002 and 2009. METHODS: HPV fluorescence in situ hybridization (FISH) and p16(INK4a) immunohistochemistry (p16 IHC) were performed. Results were compared with survival, age, race, gender, tobacco use, alcohol use, and nodal stage. RESULTS: Twenty-five patients met the inclusion criteria, of whom 88% were >10 pack year tobacco users. Twenty-eight percent were HPV-positive defined by both p16+ and FISH+. Five-year overall survival was 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .35). Similarly, 5-year disease-free survival rates were 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .54). All 3 HPV-positive nonsmokers were survivors, but this was not significant because of the small sample size (P > .05). No other characteristics were associated with survival (P > .05). CONCLUSION: Twenty-eight percent of metastatic lymph nodes from occult primary tumors were HPV positive. There was no survival difference associated with HPV status. Most of the HPV-positive patients in this study were tobacco users who had similar survival to HPV-negative patients, so caution should be used in interpreting HPV status in these patients.

Sinonasal teratocarcinosarcoma with yolk sac elements: a neoplasm of somatic or germ cell origin?

Sinonasal teratocarcinosarcoma is an uncommon, aggressive, morphologically heterogenous tumor composed of cells derived from the 3 somatic layers. A histogenetic origin from a multipotential adult somatic stem cell with divergent differentiation has been favored over a germ cell origin. This assumption has been based on the lack of germ cell elements and, until recently, the absence of demonstrable amplification of 12p. We report a case that exhibited foci of yolk sac elements with papillary structures and intracytoplasmic periodic acid-Schiff-positive, diastase-resistant, α-fetoprotein-positive, hyaline globules. An expanded area of undifferentiated cells, likely precursor cells, in the basal layer of the overlying mucosal epithelium transitions into and merges with the immature epithelial, neuroepithelial, and mesenchymal components. These previously unreported histomorphological features support the hypothesis that this tumor is a teratomatous tumor arising from pluripotent embryonic stem cells in the basal layer of the sinonasal epithelium. That notion is further supported by fluorescence in situ hybridization cytogenetic analysis, which showed a distinct subpopulation of the tumor cells with an extra copy of chromosome 12p13.

Role of cytopathology in cancer control in low-resource settings: sub-Saharan Africa's perspective.

Cancer is an emerging public health problem in Africa especially with increasing exposure to risky life styles, environmental carcinogens and emergence of AIDS-associated cancers. Of the WHO estimated 7.9 million cancer-related deaths in 2007 more than 72% occurred in the low- and middle-income countries and 80% presented in the late stages. To implement the WHO resolution on cancer control programs in these settings, feasible evidence-based interventions for prevention, early diagnosis and detection need to be widely introduced. Fundamental to appropriate cancer treatment and statistics is accurate diagnosis. In low-resource settings, the diagnostic techniques and procedures should be reliable, cost-effective, simple and acceptable to patients. In addition, the required equipment should be affordable, requiring minimal maintenance and with readily available consumables. Cytology, as a simple standardized low-technology procedure, fulfills these criteria and is most effective in addressing the major components of cancer control programs in these areas. The major obstacles to its widespread establishment are lack of awareness and inadequate numbers of trained personnel compounded by sociopolitical factors, poor national planning and implementation. Rather than investing in new technology or alternative screening methods, efforts should focus on the education and training of local personnel, as feasible options, to improve the chances of implementing meaningful cancer control programs.

Cytomorphology, ultrastructural, and cytogenetic findings in follicular dendritic cell sarcoma: a case report.

BACKGROUND: Follicular dendritic cell (FDC) sarcoma is a rare low-to-intermediate grade malignant dendritic cell neoplasm that often has an indolent clinical course. FDC sarcomas are often misdiagnosed on aspiration cytology. CASE: A 26-year-old woman presented with a solid, slowly growing, painless mass in her right neck for 3 months. Computed tomography revealed a 3.6-cm, well-defined homogenous solid mass located posterior to the mandible and submandibular glands. Fine needle aspiration cytology revealed many large, spindle to ovoid epithelioid cells in singles, small clusters, and syncytial sheets with moderate to abundant cytoplasm, indistinct cell borders, irregular nuclear membrane, fine to vesicular chromatin, and conspicuous nucleoli. The background contained many small mature lymphocytes intimately mixed with large epithelioid tumor cells. Tumor cells were strongly positive for CD21, CD35, CD23, and fascin. Diagnosis of FDC sarcoma was rendered; follow-up surgical resection and ultrastructural study confirmed the diagnosis. The cytogenetic study showed a normal female karyotype 46,XX. CONCLUSION: Although the cytomorphology of FDC sarcoma is characteristic, a preoperative diagnosis of FDC sarcoma based on fine needle aspiration cytology is very challenging, if not impossible. Immunohistochemistry is always necessary for rendering and/or confirming the diagnosis, and ultrastructural studies are helpful.

The role of routine immunohistochemistry for Helicobacter pylori in gastric biopsy.

Helicobacter pylori infection is associated with gastritis, gastric ulcer, gastric adenocarcinoma, and mucosal associated lymphoid tissue lymphoma. Documenting the presence of H pylori in a gastric biopsy is essential for appropriate patient care. Several special stains and immunohistochemistry (IHC) stain for H pylori are available, and many laboratories are routinely using one of them. We introduced routine IHC for H pylori about a year ago, and this study aims to investigate the value of this protocol. A total of 224 patients qualified for the study criteria during this period. The diagnoses were chronic active gastritis (68), chronic gastritis (76), no pathologic abnormality (50), reactive gastropathy (24), and polyps (6). Fifty-four cases were positive for H pylori on IHC, including 50 chronic active gastritis and 4 chronic gastritis. The IHC positive rate was 73.5% (50/68) in chronic active gastritis, 5.3% (4/76) in chronic gastritis, and 0% (0/80) in other diagnoses. The sensitivity/specificity of finding H pylori by blindly reviewing hematoxylin and eosin slides was 100%/100%, 100%/100%, 95%/100%, and 100%/100% from the 4 authors. Our results showed that many gastric biopsies (35.7%, 80/224) had no pathologic abnormality or reactive gastropathy and did not need a routine IHC for H pylori. Hematoxylin and eosin slide review had a very good sensitivity and specificity with all levels of observers. In summary, IHC for H pylori should not be routinely used, especially during these economically challenging times. Immunohistochemistry should be reserved for unexplained gastritis and previously treated patients with likely low organism density.

Geographic variation in the prevalence of Kaposi sarcoma-associated herpesvirus and risk factors for transmission.

BACKGROUND: The aim of the present study was to estimate the prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in the female general population, to define geographic variation in and heterosexual transmission of the virus. METHODS: The study included 10,963 women from 9 countries for whom information on sociodemographic characteristics and reproductive, sexual, and smoking behaviors were available. Antibodies against KSHV that encoded lytic antigen K8.1 and latent antigen ORF73 were determined. RESULTS: The range of prevalence of KSHV (defined as detection of any antigen) was 3.81%-46.02%, with significant geographic variation noted. In Nigeria, the prevalence was 46.02%; in Colombia, 13.32%; in Costa Rica, 9.81%; in Argentina, 6.40%; in Ho Chi Minh City, Vietnam, 15.50%; in Hanoi, Vietnam, 11.26%; in Songkla, Thailand, 10%; in Lampang, Thailand, 8.63%; in Korea, 4.93%; and in Spain, 3.65%. The prevalence of KSHV slightly increased with increasing age among subjects in geographic areas where the prevalence of KSHV was high, such as Nigeria and Colombia, and it significantly decreased with increases in the educational level attained by subjects in those areas. KSHV was not statistically associated with age at first sexual intercourse, number of sex partners, number of children, patterns of oral contraceptive use, presence of cervical human papillomavirus DNA, or smoking status. CONCLUSIONS: The study provides comparable estimates of KSHV prevalence in diverse cultural settings across 4 continents and provides evidence that sexual transmission of KSHV is not a major source of infection in the general population.

Intracranial extraskeletal mesenchymal chondrosarcoma.

Intracranial extraskeletal mesenchymal chondrosarcoma is a rare malignant variant of chondrosarcomas. We present a 5-year-old Saudi male child who was brought to the Emergency Department with the complaints of headache, irritability, vomiting, and unsteadiness of gait with right hemiparesis. Radiological studies confirmed the presence of a space-occupying lesion in the left cerebral hemisphere of the brain. Through a left temporoparietal craniotomy a total macroscopic excision of the tumor was carried out, and the tumor was found attached to the dura at the base of the temporal fossa. The tumor was well circumscribed, extra axial in location, and was easily dissected from the other part of the brain. The histopathological examination revealed the tumor to be a mesenchymal chondrosarcoma. This rare tumor of the pediatric age group should be included in the differential diagnosis of all intracranial tumors with aggressive characteristics.