Stimulated whole salivary flow rate: The most appropriate technique for assessing salivary flow in Sjögren syndrome.

BACKGROUND: We sought to determine the most appropriate method for measuring salivary flow to aid the diagnosis of Sjögren's syndrome (SS). Specifically, we compared the unstimulated whole salivary flow rate (UWSFR) with the stimulated whole salivary flow rate (SWSFR). MATERIAL AND METHODS: This case-control study comprised one group of 103 patients with SS and a control group of 50 healthy people. We measured the UWSFR and SWSFR in both groups according to the guidelines established by Navacet [1993]. RESULTS: The UWSFR and SWSFR were significantly lower in the patient group compared with the controls (p < 0.01). Among the participants in the patient group, we found a decreased UWSFR in 84 individuals (81.5%) and a decreased SWSFR in 90 individuals (87.4%). We encountered difficulties obtaining saliva in 37 (35.9%) patients during the UWSFR test, and in 12 (11.7%) patients during the SWSFR test. There was no significant statistical difference in the UWSFR or SWSFR between patients with primary and secondary SS. CONCLUSIONS: Compared with the UWSFR, the SWSFR is a more suitable and effective method for measuring salivary flow in patients with SS, as well as for qualitative analysis of the obtained saliva.

Ecocardiografía transesofágica intraoperatoria en cirugía cardiovascular. Documento de consenso de la Sociedad Española de Anestesiología y Reanimación (SEDAR) y Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE) / Intraoperative transesophageal echocardiography in cardiovascular surgery. Consensus document from the Spanish Society of Anesthesia and Critical Care (SEDAR) and the Spanish Society of Endovascular and Cardiovascular Surgery (SECCE)

La ecocardiografía transesfofágica es una técnica semiinvasiva que permite una evaluación de la morfología y función cardiaca a tiempo real y que constituye, a día de hoy, un estándar de calidad en las intervenciones de cirugía cardiovascular. Se ha convertido en una herramienta fundamental tanto de monitorización como de diagnóstico en el perioperatorio que permite la correcta planificación quirúrgica y manejo farmacológico dirigido. El objetivo de este documento es dar respuesta de forma consensuada y avalada por la evidencia científica de cuándo y cómo debe hacerse la ecocardiografía transesfofágica intraoperatoria en cirugía cardiovascular, qué aplicaciones tiene en el intraoperatorio, quién debe realizarla y cómo debe transmitirse la información obtenida durante el estudio. Los autores han hecho una revisión sistemática de las guías internacionales, artículos de revisión y ensayos clínicos para dar respuesta a estas preguntas

Transesophageal echocardiography is a semi-invasive technique that allows an evaluation of cardiac morphology and function in real time and it is a quality standard in cardiovascular surgery. It has become a fundamental tool for both monitoring and diagnosis in the intraoperative period that allows decide the correct surgical planning and pharmacological management. The goal of this document is to answer the questions of when and how the perioperative TEE should be performed in cardiovascular surgery, what are their applications in the intraoperative, who should perform it and how the information should be transmitted. The authors made a systematic review of international guidelines, review articles and clinical trials to answer by consensus to these questions

Intraoperative transesophageal echocardiography in cardiovascular surgery. Consensus document from the Spanish Society of Anesthesia and Critical Care (SEDAR) and the Spanish Society of Endovascular and Cardiovascular Surgery (SECCE). / Ecocardiografía transesofágica intraoperatoria en cirugía cardiovascular. Documento de consenso de la Sociedad Española de Anestesiología y Reanimación (SEDAR) y Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE).

Transesophageal echocardiography is a semi-invasive technique that allows an evaluation of cardiac morphology and function in real time and it is a quality standard in cardiovascular surgery. It has become a fundamental tool for both monitoring and diagnosis in the intraoperative period that allows decide the correct surgical planning and pharmacological management. The goal of this document is to answer the questions of when and how the perioperative TEE should be performed in cardiovascular surgery, what are their applications in the intraoperative, who should perform it and how the information should be transmitted. The authors made a systematic review of international guidelines, review articles and clinical trials to answer by consensus to these questions.

Association between maxillary sinus pathology and odontogenic lesions in patients evaluated by cone beam computed tomography. A systematic review and meta-analysis.

BACKGROUND: A study is made of the association between maxillary sinus pathology and odontogenic lesions in patients evaluated with cone beam computed tomography. MATERIAL AND METHODS: A literature search was made in five databases and OpenGrey. Methodological assessment was carried out using the Newcastle-Ottawa tool for observational studies. The random-effects model was used for the meta-analysis. RESULTS: Twenty-one studies were included in the qualitative review and 6 in the meta-analysis. Most presented moderate or low risk of bias. The periodontal disease showed to be associated with the thickening of the sinus membrane (TSM). Mucous retention cysts and opacities were reported in few studies. The presence of periapical lesions (PALs) was significantly associated to TSM (OR=2.43 (95%CI:1.71-3.46); I2=34.5%) and to odontogenic maxillary sinusitis (OMS) (OR=1.77 (95%CI: 1.20-2.61); I2=35.5%). CONCLUSIONS: The presence of PALs increases the probability of TSM and OMS up to 2.4-fold and 1.7-fold respectively. The risk differences suggests that about 58 and 37 of out every 100 maxillary sinuses having antral teeth with PALs are associated with an increased risk TSM and OMS respectively. The meta-evidence obtained in this study was of moderate certainty, and although the magnitude of the observed associations may vary, their direction in favor sinus disorders appearance, would not change as a result.

Biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw: A systematic review.

BACKGROUND: The goal of this paper was to identify available biomarkers to predict the onset of biphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: Case-control studies comparing the different concentrations of a series of molecules detected in serum and urine as matrices of BRONJ affected patients vs. non-affected were included. PRISMA guidelines for systematic reviews were used for the present paper. Two reviewers independently screened electronic databases (Medline, Web of science, and The Cochrane Library) and performed hand searches. Risk of bias assessment of selected studies was performed by the Newcastle-Ottawa Scale. This study is registered as PROSPERO CRD42017078149. RESULTS: From a total of 601 identified studies, 7 (4 articles with high methodological quality and 3 with medium) articles were included. They investigate 2623 patients, of whom 91 (3.47%) developed BRONJ. A total of 7 biomarkers were identified and classified into 3 groups: bone turnover, angiogenesis and endocrine markers. Conflicting results were found in relation to most biomarkers. CONCLUSIONS: The present review suggests that no useful markers are currently available to evaluate BRONJ risk. Nevertheless, the present paper indicates that a paradigm shift from bone turnover biomarkers to angiogenesis and endocrine markers could shed light on this search.

Oral mucous membrane pemphigoid: A clinical study of 100 low-risk cases.

OBJECTIVE: To analyze the severity of the oral lesions in low-risk oral mucous membrane pemphigoid (OMMP) measured according to the size of the bullous areas and the number of simultaneously affected oral locations. MATERIAL AND METHODS: A total of 100 cases of low-risk OMMP were studied. The symptoms and location of OMMP in the oral cavity were analyzed. The bullous areas were measured, establishing three grades according to the greatest bullous lesion size (grade 1: < 3 cm in size; grade 2: 3-6 cm; and grade 3: > 6 cm). RESULTS: The mean age of the patients was 66.07 ± 13.55 years, with a clear predominance of females (84%). Desquamative gingivitis was the most common presentation (97%). A single oral location was found in 67% of the cases, two in 18% and three in 15%. The most common presentation corresponded to grade 1 (the greatest bullous lesion size < 3 cm; 51.6% of the cases). CONCLUSIONS: Most cases of low-risk OMMP are restricted to a single site in the oral cavity, the gingiva being the most common location-the predominant grade corresponding to the greatest bullous lesion size < 3 cm.

Periodontal, salivary and IL-6 status in rheumatoid arthritis patients. A cross-sectional study.

BACKGROUND: The aim of this study was to determine whether saliva interleukin-6 (IL-6) levels are elevated in patients with rheumatoid arthritis versus a control group and examine the possible relationship between the oral condition and the risk of RA. MATERIAL AND METHODS: In 30 patients with RA and 30 healthy controls, different periodontal indices were recorded; sialometric measurements were taken to determine resting whole saliva, stimulated whole saliva and stimulated parotid saliva flow; and the saliva IL-6 levels were measured. Logistic regression analysis was performed, with the presence or absence of RA as dependent variable. RESULTS: The patients with RA had a greater presence of bacterial plaque, a greater periodontal pocket depth, a larger percentage of medium-sized pockets, and greater periodontal attachment loss compared with the controls. Likewise, a decrease in resting and stimulated saliva flow was observed, together with an increase in saliva IL-6 levels. Logistic regression analysis reported that the plaque index is the principal differentiating factor of patients with RA. Stimulated parotid saliva flow was also significantly correlated to the presence of RA. CONCLUSIONS: The patients with RA showed a greater tendency to develop periodontal disease than the controls, with lower salivary flow and higher levels of IL-6 in saliva.

Serum levels of RANKL and OPG, and the RANKL/OPG ratio in bisphosphonate-related osteonecrosis of the jaw: Are they useful biomarkers for the advanced stages of osteonecrosis?

BACKGROUND: We determined whether serum levels of Receptor Activator for Nuclear Factor κ B Ligand (RANKL), Osteoprotegerin (OPG), and the RANKL/OPG ratio could be useful biomarkers for the severity of oral lesions in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: A case-control study in which Group 1 consisted of 41 patients with BRONJ due to intravenous bisphosphonates, and Group 2 consisted of 44 healthy control cases. The plasma levels of RANKL and OPG were analyzed by an ELISA assay. The OPG/RANKL ratio was also calculated. We determined if the mean serum values differed among the different stages of BRONJ. RESULTS: Serum levels of RANKL were lower in Group 1 than in Group 2 (p =0.01), and serum levels of OPG were higher in patients with BRONJ than in the controls (p =0.006). The ratio of RANKL/OPG was greater in the controls than in Group 1 (p >0.01). There were no significant differences in the serum levels of RANKL and OPG among the different stages of osteonecrosis (p >0.05). CONCLUSIONS: Serum levels of RANKL and OPG, and the RANKL/OPG ratio were not valuable biomarkers for determining the severity of oral lesions in patients with BRONJ.

Exposed necrotic bone in 183 patients with bisphosphonate-related osteonecrosis of the jaw: Associated clinical characteristics.

BACKGROUND: The main objective of our study was to identify oral symptoms and signs most likely to be associated with the exposure of necrotic bone in bisphosphonate-related osteonecrosis of the jaw (BRONJ). MATERIAL AND METHODS: The study group consisted of 183 patients with BRONJ. We recorded data on the underlying disease, bisphosphonate used, location of osteonecrosis, symptoms, pain, fistula development, suppuration, infection, exposed necrotic bone, and BRONJ stage. RESULTS: The mean age of the patients was 68.22 ± 12.19 years. The sample included 118 (64.5%) women. Breast cancer and multiple myeloma were the most common underlying diseases, and 50 patients received oral bisphosphonates for osteoporosis. Dental extractions (69.4%) and mandibular location (74.3%) predominated. The only two variables influencing the possibility of necrotic bone exposure were intravenous bisphosphonate administration and the presence of an intraoral fistula (p < 0.05). CONCLUSIONS: Intravenous bisphosphonate use and intraoral fistula presence were associated with a major predisposition to bone exposure in patients with BRONJ.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Grade of sclerosis in the contralateral mandibular area in osteonecrosis of the jaws.

The objective of this study was to compare the grade of radiographic sclerosis between the area of osteonecrosis and the at-risk contralateral mandibular area without osteonecrosis. Three groups were studied: group 1 comprised 30 cases of medication-related osteonecrosis of the jaws (MRONJ); group 2 was the healthy contralateral area without osteonecrosis of the group 1 cases; group 3 comprised 30 healthy controls. ImageJ software was used to analyze the computed tomography images, and the grade of bone sclerosis was compared between the three groups. The grade of sclerosis was significantly higher in group 1 than in the other groups (P<0.05); the difference between groups 2 and 3 was not significant. Sclerosis was significantly greater in the area of bone necrosis than in the contralateral mandibular area in patients with MRONJ. No significant differences were found in the grade of sclerosis between the contralateral non-affected mandibular area of patients with MRONJ and the control patients.

Effect of nonsurgical periodontal treatment in patients with periodontitis and rheumatoid arthritis: A systematic review.

BACKGROUND: Periodontitis has been regarded as a potential risk factor for rheumatoid arthrosis (RA). A systematic review is made to determine whether nonsurgical periodontal treatment in patients with RA offers benefits in terms of the clinical activity and inflammatory markers of the disease. MATERIAL AND METHODS: A search was made of the Medline-PubMed, Cochrane, Embase and Scopus databases to identify studies on the relationship between the two disease processes, and especially on the effects of nonsurgical treatment in patients of this kind. The search was based on the following keywords: rheumatoid arthritis AND periodontitis (MeSH), rheumatoid arthritis AND periodontal treatment. RESULTS: Eight articles on the nonsurgical treatment of patients with periodontitis and RA were finally included in the study. All of them evaluated clinical (DAS28) and laboratory test activity (ESR, CRP, IL-6, TNFα) before and after treatment. A clear decrease in DAS28 score and ESR was recorded, while other parameters such as CRP, IL-6 and TNFα showed a nonsignificant tendency to decrease as a result of treatment. CONCLUSIONS: Nonsurgical treatment improved the periodontal condition of patients with periodontitis and RA, with beneficial effects upon the clinical and laboratory test parameters (DAS28 and ESR), while other inflammatory markers showed a marked tendency to decrease. However, all the studies included in the review involved small samples sizes and follow-up periods of no more than 6 months. Larger and particularly longitudinal studies are therefore needed to more firmly establish possible significant relations between the two disease processes.

Concept, diagnosis and classification of bisphosphonate-associated osteonecrosis of the jaws. A review of the literature.

BACKGROUND: Bisphosphonates (BPs) and other antiresorptive agents such as denosumab are widely prescribed for the treatment of osteoporosis and are also used in patients with multiple myeloma and metastatic breast or prostate cancer for avoiding bone reabsorption and fractures that result in increased morbidity-mortality among such individuals. MATERIAL AND METHODS: We made a bibliographic search to analyze the concept, diagnosis and the different classifications for bisphosphonate-associated osteonecrosis of the jaws. RESULTS: Osteonecrosis of the jaws (ONJ) is an important complication of exposure to BPs or other antiresorptive agents, and although its prevalence is low, it can pose management problems. The definition, diagnosis and classification of osteonecrosis have evolved since Marx reported the first cases in 2003. CONCLUSIONS: The present study offers a literature review and update on the existing diagnostic methods and classification of the disorder, with a view to facilitating earlier and more effective treatment.

Medication-related osteonecrosis of the jaw associated with bisphosphonates and denosumab in osteoporosis.

OBJECTIVE: To describe the clinical characteristics and evolution of our series of medication-related osteonecrosis of the jaws (MRONJ) associated with denosumab in osteoporotic patients. MATERIAL AND METHODS: We present 10 new cases of MRONJ in patients receiving denosumab for osteoporosis. We describe the mean doses of denosumab, previous bisphosphonate intake, and the clinical characteristics associated with the osteonecrosis, such as local contributing factors, symptoms, and evolution after treatment. RESULTS: The mean number of denosumab doses was 3.4 ± 2.2. In 90% of patients, there was a prior history of oral bisphosphonate intake, with a mean duration of 46.78 ± 25.11 months. The most common local factor was dental extraction (6 cases; 60%), and most cases had necrotic bone exposure (9/10, 90%). Sclerosis of the bone was the most common radiographic finding. Stage 1 was the most common ONM stage, found in 80%. 'Cure' after conservative treatments was obtained in 71.4%. CONCLUSIONS: Most of our cases were in the early stages of MRONJ, and the success rate after conservative treatment was high.

Mitoxantrone as a contributing factor in medication-related osteonecrosis of the jaws.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is usually initiated by dental surgery, but is occasionally exacerbated by other antiresorptive (denosumab) and anti-angiogenic therapies, and in such cases is currently termed medication-related osteonecrosis of the jaws (MRONJ). The case of a 58-year-old female with breast cancer who developed multiple and ultimately fatal metastases despite 3 years of treatment with chemotherapeutic drugs and intravenous bisphosphonates, is presented herein. Her malignant disease worsened and she was started on mitoxantrone. She developed a severe adverse reaction to this drug soon after starting treatment. As well as diarrhoea and vomiting, she had a very aggressive gingival inflammation with multiple ulcerations in both jaws and wide areas of necrotic bone, affecting the attached gingiva, and seemingly unrelated to dental plaque. These ulcerations and the exposed necrotic bone persisted for more that 6 months, until her death. This report describes a case in which severe gingival ulcerations that occurred after mitoxantrone treatment for metastatic breast cancer were a local factor that initiated MRONJ.

Complement activation product C4d in oral and oropharyngeal squamous cell carcinoma.

OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal-adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 ± 0.07 vs 0.04 ± 0.03 µg ml(-1) , P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 ± 0.59 vs 1.09 ± 0.39 µg ml(-1) , P = 0.232). CONCLUSION: C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC.

Sclerosis in bisphosphonate-related osteonecrosis of the jaws and its correlation with the clinical stages: study of 43 cases.

We analysed the degree of sclerosis in the different stages of bisphosphonate-related osteonecrosis of the jaws (BRONJ) and studied the relation between the grade of sclerosis, the clinical symptoms, and the depth of lucency. We compared 43 patients with mandibular BRONJ with a control group of 40 cases with no bony lesions. The presence of sclerotic bone, cortical irregularities, radiolucency, fragmentation or sequestration, periostitis, and narrowing of the mandibular canal were studied from computed tomographic (CT) scans using the program ImageJ 1.47v (National Institute of Health, Bethesda, USA) to measure the radiolucency, width of the cortices, and degree of sclerosis. Patients with BRONJ had more severe sclerosis than controls (p<0.01). There was also a significant difference among the different stages of BRONJ, with the highest values found in stage III (p=0.02). The degree of sclerosis differed according to sex, type of bisphosphonate, and the clinical characteristics such as pain, or suppuration, but not significantly so (p>0.05). We conclude that the degree of sclerosis increases with the clinical stage of BRONJ, and is correlated with the depth of lucency.

Retrospective case-control study of viral pathogen screening in proliferative verrucous leukoplakia lesions.

OBJECTIVE: This study aimed to survey the presence of known oncoviruses in oral biopsies from patients diagnosed with the aetiologically undetermined proliferative verrucous leukoplakia and compare results to those from milder oral leukoplakia (OL) cases, oral squamous cell carcinoma, a common outcome of the lesions of interest, and healthy controls. DESIGN: Blind, retrospective, case-control study. SETTING: A stomatology unit in an academic Hospital and a Public Health laboratory. PARTICIPANTS: Forty patients were divided in four groups. Ten patients had been diagnosed with proliferative verrucous leukoplakia, 10 with OL and 10 with OSCC, and 10 were healthy subjects. MAIN OUTCOME MEASURES: The presence or absence of oncovirus DNA was assayed with the amplification of viral genetic markers using PCR and subsequent gel electrophoresis confirmation. Amplified fragments were sequenced and identified bioinformatically. RESULTS: No DNA from the herpesvirus, papillomavirus or polyomavirus species was detected in the samples. CONCLUSIONS: No association between proliferative verrucous leukoplakia and target viruses was detected. A higher throughput viral metagenomic approach may prove valuable for future analyses, as it would not be restricted to a priori knowledge of potential targets.

Interleukin-6 concentration changes in plasma and saliva in bisphosphonate-related osteonecrosis of the jaws.

AIM: To determine the plasma and saliva levels of IL-6 in patients with bisphosphonate-related osteonecrosis of the jaws (BRONJ) and to investigate whether there is a correlation between more advanced stages of BRONJ and levels of IL-6. MATERIAL AND METHODS: We studied three groups: group 1 consisted of 30 patients with BRONJ due to intravenous bisphosphonates (ivBP), group 2 consisted of 25 patients treated with ivBP but without BRONJ, and group 3 consisted of 15 healthy controls. In each case, we assayed plasma and saliva IL-6 samples using an ELISA test. RESULTS: Significantly, higher IL-6 values were found in both saliva and plasma in group 1 vs groups 2 and 3 (P < 0.01). Group 1 showed no differences in plasma or saliva IL-6 according to patient gender (P > 0.05), type of tumor, BRONJ location, etiology of BRONJ, or disease stage (P > 0.05). We found higher plasma and saliva IL-6 values in the more advances stages of BRONJ, although the differences were not statistically significant. CONCLUSIONS: Plasma and saliva IL-6 values were higher in our patients with BRONJ than in controls and therefore might be a useful tool for monitoring the severity of BRONJ.

Urban legends series: oral leukoplakia.

To date, the term oral leukoplakia (OL) should be used to recognize 'predominantly white plaques of questionable risk, having excluded (other) known diseases or disorders that carry no increased risk of cancer'. In this review, we addressed four controversial topics regarding oral leukoplakias (OLs): (i) Do tobacco and alcohol cause OLs?, (ii) What percentage of OLs transform into oral squamous cell carcinoma (OSCC)?, (iii) Can we distinguish between premalignant and innocent OLs?, and (iv) Is proliferative verrucous leukoplakia (PVL) a specific entity or just a form of multifocal leukoplakia? Results of extensive literature search suggest that (i) no definitive evidence for direct causal relationship between smoked tobacco and alcohol as causative factors of OLs, (ii and iii) the vast majority of OLs follow a benign course and do not progress into a cancer, and no widely accepted and/or validated clinical and/or biological factors can predict malignant transformation, and (iv) the distinction between multifocal/multiple leukoplakias and PVL in their early presentation is impossible; the temporal clinical progression and the high rate of recurrences and development of cancer of PVL are the most reliable features for diagnosis.