Immunohistochemical profile of the pulmonary vasculature in subjects with cirrhosis and histopathologic evidence of pulmonary vascular disease: An autopsy study.

Portopulmonary hypertension (POPH) is a complication of cirrhosis that results in right ventricular failure and death. The objective of this autopsy investigation was to compare pulmonary arterial receptors in subjects with cirrhosis and histopathologic evidence of pulmonary vascular disease (PVD) and control group subjects with cirrhosis lacking evidence of PVD. Autopsy records of 824 subjects with cirrhosis were reviewed to identify pulmonary arterial vasculopathy. Lung sections from paraffin embedded blocks were immunostained for endothelin A (ET-A), endothelin B (ET- B), estrogen α (ER-α), estrogen ß (ER-ß), and vascular endothelial growth factor (VEGF). Subjects with cirrhosis and histopathologic evidence of PVD included 27 individuals with intimal hyperplasia (93%), medial hypertrophy (96%), and plexiform lesions (78%). Immunohistochemical staining for ET-A revealed positive reactivity in 40% of the group with cirrhosis and histopathologic evidence of PVD and 13% of the control group (NS). ET-B reactivity in the pulmonary endothelium and smooth muscle was identified in all subjects with cirrhosis and histopathologic evidence of PVD and control group. VEGF reactivity was identified in the endothelium in all subjects with cirrhosis and histopathologic evidence of PVD compared with 33% of the control group (p = 0.0002). ER-ß reactivity was observed in four subjects (26.6%) with cirrhosis and histopathologic evidence of PVD while none in the control group (NS). Cirrhosis and histopathologic evidence of PVD was found in 3.3% of autopsies with the pulmonary vasculature immunohistochemical profile demonstrating endothelial and smooth muscle reactivity for endothelin, VEGF and ER-ß.

Metastatic Basal Cell Carcinoma: An Unexpected Diagnosis in a Young Patient With Back Pain.

ABSTRACT: Basal cell carcinoma (BCC) portends a notoriously favorable prognosis in most patients with morbidity limited to localized destruction and recurrence. Metastatic BCC (mBCC) is an unexpected outcome affecting less than 1% of patients with a known primary lesion and predominantly involves regional lymph nodes. Reports of isolated bone involvement and spinal cord compression are rare. In the cases we identified in the literature, patients presented with massive primary lesions on the trunk that had been present for years and that were often still present at the time of diagnosis. Additionally, histology of distant metastatic lesions typically reveals aggressive subtypes. Herein, we report a case of mBCC in a patient with a history of BCC involving the cheek; the lesion was excised more than 10 years ago. He was referred to our institution for acutely worsening back pain and multifocal neurologic deficits. Clinical symptoms and radiographic findings demonstrated isolated bone involvement, with multiple lytic bone lesions and spinal cord compression noted on imaging studies. Biopsy revealed nests of small basaloid cells with peripheral palisading and immunohistochemical staining consistent with the unexpected diagnosis of mBCC, nodular subtype. Our case illustrates that a historically resected primary lesion may cause distant metastasis after a decade and that nonaggressive subtypes can also be implicated. We also provide insight into the potential pathogenesis of this manifestation.

Solitary Metastasis of Colon Adenocarcinoma Mimicking Colloid Cyst of the Third Ventricle.

Metastatic lesions to the choroid plexus, although far less common than colloid cysts, can present very similarly both symptomatically and radiographically. Choroid plexus metastases are most common in the lateral ventricles, however, when they occur in the third and fourth ventricles they may cause obstructive hydrocephalus typical of a colloid cyst lesion. Renal cell carcinoma is the most common primary cancer, but many rare primaries have been reported. When patients are presenting with symptoms typical of colloid cysts it is important to consider past oncological history and if past medical history is significant for cancer using MR spectroscopy may be valuable in distinguishing between cystic and metastatic lesions.

A Rare Case of Ecchordosis Physaliphora Presenting With Headache, Abducens Nerve Palsy, and Intracranial Hypertension.

We report a rare case of ecchordosis physaliphora presenting with headache, nausea, and diplopia. On neurological examination, the patient was found to have left abducens nerve palsy. CT of the head without contrast was unremarkable. Brain MRI demonstrated a non-enhancing retroclival mass with a mass effect upon the ventral pons. The mass had increased signal intensity on T2 and decreased signal intensity on T1-weighted sequences. Lumbar puncture revealed an opening pressure of 37 cm H2O. The patient underwent an endoscopic endonasal approach for retroclival mass resection three weeks later. The tissue analysis of the mass was consistent with ecchordosis physaliphora. This could have been misdiagnosed as idiopathic intracranial hypertension had the MRI of the brain not been performed.

L5 Fracture Dislocation Secondary to Cold Abscess Treated by Posterior Corpectomy With Expandable Cage Placement.

Infections of the lumbar spine can have serious sequelae, including neurological deficits, paralysis, and death. Prolonged infection can result in fracture of the vertebrae, local abscesses, and infiltration and compression of local vascular structures. In cases with significant instability or neurological compromise, a common treatment approach is vertebral corpectomy with interbody cage followed by long-term antibiotics. The following case describes a patient with a three-month history of progressively worsening lower back pain, lower extremity radiculopathy, and bilateral lower extremity edema, in the setting of a nontraumatic three-column fracture dislocation of L5 with grade 4 retrolisthesis of L4 on L5. A posterior-only corpectomy with placement of an expandable cage, to be followed by pedicle screw placement from L3-S1/ilium, was performed. The procedure was successful, and the patient was discharged on postoperative day 5 without complication and with resolution of his edema. Histopathological analysis demonstrated acute and chronic inflammation, but extensive tests and cultures failed to identify a causative organism. This case highlights several interesting features, including a technically challenging and seldom-performed procedure, as well as the ability of lumbar spinal infections to present with leg edema due to involvement the inferior vena cava and iliac vessels. For patients with three-column fractures of L5 due to an inflammatory process or trauma, a single-stage posterior corpectomy with placement of an expandable cage may be considered as an appropriate treatment option.

A Case of Previously Unsuspected Cardiac Sarcoidosis Diagnosed at Autopsy and 23-Year Review of One Institution's Sarcoidosis Deaths.

Sarcoidosis is a noncaseating granulomatous disease of unknown etiology. The incidence is 11 per 100 000 white individuals and 34 per 100 000 black individuals. Cardiac involvement is seen in 2% to 5% of patients with systemic sarcoidosis and is often clinically undetected. This may be due to relative rarity of cardiac involvement, variability in presentation, or that there are no good clinical criteria for the diagnosis of cardiac sarcoidosis. Patients may be totally asymptomatic or have heart block, myocardial infarctions, heart failure, or sudden cardiac death, which may be due to involvement of the conduction system by sarcoidosis. We present a case of a 54-year-old black male with hypertension and hyperlipidemia. Prior to his death, he was witnessed to suddenly stand up, grab his chest, and collapse. His clinical cause of death was hypertensive and atherosclerotic cardiovascular disease. A retrospective review of autopsy cases over the last 23 years (1995-2018) at our institution (n = 6900) was undertaken. This case illustrates a rare disease and highlights the importance of complete autopsy even in patients who might otherwise be signed out as an external exam or records review only.

ATRX protein loss and deregulation of PI3K/AKT pathway is frequent in pilocytic astrocytoma with anaplastic features.

INTRODUCTION: Pilocytic astrocytoma (PA) with anaplastic features (PAAF) is a rare entity associated with decreased survival. It is characterized by hypercellularity, atypia, brisk mitotic activity, variable necrosis, and association with a classic PA component or anaplastic transformation in a recurrent tumor with a previously-documented classic PA. MATERIALS AND METHODS: We present 5 PAAF cases with clinical, radiological, pathological, and molecular correlation. We interrogated ATRX, IDH, TP53, PTEN, EGFR, BRAF, 6q23, p16(Ink4a) by sequencing, FISH, and immunohistochemistry. RESULTS: Four tumors were located in the cerebellum, and 1 was supratentorial. All showed ATRX protein loss by immunohistochemistry, loss of heterozygosity for PTEN, and had no IDH/TP53/BRAF mutations, nor EGFR amplification. Two of 5 tumors showed BRAF duplication by pyrosequencing. All showed loss of PTEN nuclear expression in subsets of tumor cells, which was associated with variable cytoplasmic positivity for pS6. There was a relative correlation between loss of PTEN expression and pS6 cytoplasmic expression. p53 was expressed in ~ 50% of tumor cells in all tumors. P16 was variably lost in all cases. One tumor showed MYB/6q23 deletion. CONCLUSION: We confirm ATRX protein loss suggestive of ATRX alteration as well as dysregulation of the PI3K/AKT pathway and, less often, of the MAPK/ERK pathway in PAAF.
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Plexiform Schwannoma of the Tongue in a Pediatric Patient with Neurofibromatosis Type 2: A Case Report and Review of Literature.

INTRODUCTION: Plexiform schwannoma is a rare variant of schwannoma that accounts for only 5% of all schwannomas. Herein, we present a rare case of plexiform schwannoma of the tongue in a pediatric patient with neurofibromatosis type 2 (NF2). CASE PRESENTATION: A 13-year-old female presented with a growing left-sided tongue mass. The patient has a past medical history of NF2. The tongue mass was excised and histopathological examination revealed a spindle cell tumor with multinodular growth pattern, with Verocay bodies' formation. Tumor cells were strongly positive for S-100 protein and negative for smooth muscle actin (SMA), and EMA highlighted perineural fibroblasts surrounding tumor nodules. These findings were diagnostic of plexiform schwannoma. CONCLUSION: Plexiform schwannoma of the tongue is an extremely rare tumor seen in patients with NF2. Clinical examination and histopathological evaluation are important for diagnosis of plexiform schwannoma.

Characterization of a murine model of non-lethal, symptomatic dengue virus infection.

The mosquito-borne disease dengue is caused by four serologically- and genetically-related viruses, termed DENV-1 to DENV-4. Historical setbacks due to lack of human-like mouse models of dengue were partially remedied with characterization of lethal DENV-2 infection in immunocompromised AG129 mice (deficient in IFN-α/ß/γ receptors). Recently, our group established lethal AG129 mouse infection models of DENV-1, DENV-3, and DENV-4 using human isolates. Here we compare a non-lethal, disseminated model of DENV-3 infection using strain D83-144 to that of the lethal outcome following infection by strain C0360/94. Both strains belong to DENV-3 genotype II and differ by only 13 amino acids. Intraperitoneal inoculation of AG129 mice with strain D83-144 led to clinical signs of dengue infection, such as cytokine induction, thrombocytopenia, and systemic infection. However, C0360/94 infection led to features of severe human dengue, including coagulopathy and lethal outcome, whereas D83-144 infection does not. This study is the first to investigate a low passage, non-mouse lethal strain in AG129 mice and demonstrates that D83-144 infection induces milder features of human dengue than those induced by lethal C0360/94 infection. The results suggest that the AG129 mouse model has applications to investigate factors associated with mild or severe disease.

A lethal model of disseminated dengue virus type 1 infection in AG129 mice.

The mosquito-borne disease dengue is caused by four serologically and genetically related flaviviruses termed DENV-1 to DENV-4. Dengue is a global public health concern, with both the geographical range and burden of disease increasing rapidly. Clinically, dengue ranges from a relatively mild self-limiting illness to a severe life-threatening and sometimes fatal disease. Infection with one DENV serotype produces life-long homotypic immunity, but incomplete and short-term heterotypic protection. The development of small-animal models that recapitulate the characteristics of the disseminated disease seen clinically has been difficult, slowing the development of vaccines and therapeutics. The AG129 mouse (deficient in interferon alpha/beta and gamma receptor signalling) has proven to be valuable for this purpose, with the development of models of disseminated DENV-2,-3 and -4 disease. Recently, a DENV-1 AG129 model was described, but it requires antibody-dependent enhancement (ADE) to produce lethality. Here we describe a new AG129 model utilizing a non-mouse-adapted DENV-1 strain, West Pacific 74, that does not require ADE to induce lethal disease. Following high-titre intraperitoneal challenge, animals experience a virus infection with dissemination to multiple visceral tissues, including the liver, spleen and intestine. The animals also become thrombocytopenic, but vascular leakage is less prominent than in AG129 models with other DENV serotypes. Taken together, our studies demonstrate that this model is an important addition to dengue research, particularly for understanding the pathological basis of the disease between DENV serotypes and allowing the full spectrum of activity to test comparisons for putative vaccines and antivirals.

Evacuation decision-making : Building a model to account for risk-taking preference.

One of the most stressful decisions a coastal emergency manager may face is the decision to order a large-scale evacuation for a hurricane. Even in a best-case scenario, evacuations are not a panacea. They are unpopular, expensive, disruptive and highly vulnerable to their own hazards. These issues become even more daunting when exacerbated by high populations in vulnerable areas, limited evacuation routes and a lack of nearby shelter space, which combine to create extremely long evacuation clearance times. Add forecast errors and uncertainty to these and one begins to understand the complexity of the decision-making process. These were the challenges faced by the authors as they tried to define and document the evacuation decision-making process in Lee County in Southwest Florida.

Giving new life to old lungs: methods to produce and assess whole human paediatric bioengineered lungs.

We report, for the first time, the development of an organ culture system and protocols to support recellularization of whole acellular (AC) human paediatric lung scaffolds. The protocol for paediatric lung recellularization was developed using human transformed or immortalized cell lines and single human AC lung scaffolds. Using these surrogate cell populations, we identified cell number requirements, cell type and order of cell installations, flow rates and bioreactor management methods necessary for bioengineering whole lungs. Following the development of appropriate cell installation protocols, paediatric AC scaffolds were recellularized using primary lung alveolar epithelial cells (AECs), vascular cells and tracheal/bronchial cells isolated from discarded human adult lungs. Bioengineered paediatric lungs were shown to contain well-developed vascular, respiratory epithelial and lung tissue, with evidence of alveolar-capillary junction formation. Types I and II AECs were found thoughout the paediatric lungs. Furthermore, surfactant protein-C and -D and collagen I were produced in the bioengineered lungs, which resulted in normal lung compliance measurements. Although this is a first step in the process of developing tissues for transplantation, this study demonstrates the feasibility of producing bioengineered lungs for clinical use. Copyright © 2016 John Wiley & Sons, Ltd.

A Case of Previously Unsuspected Huntington Disease Diagnosed at Autopsy.

Huntington disease (HD) is a neurodegenerative disorder with a worldwide prevalence of four to ten per 100 000. It is characterized by choreiform movements, behavioral/psychiatric disturbances, and eventual cognitive decline. Symptoms usually present between 30 and 50 years of age and the diagnosis is based on the combination of clinical symptoms, family history, and genetic testing. A variation of HD, juvenile Huntington disease (JHD), presents earlier, with more severe symptoms and with a worse prognosis. Symptoms are different in JHD, with personality changes and learning difficulties being the predominant presenting features. Seizures are common in JHD, and chorea is uncommon; movement disorders at presentation of JHD are predominantly nonchoreiform. The inheritance pattern for both HD and JHD is autosomal dominant and the disease is caused by an elongation of the CAG repeat in the huntingtin gene. There are many published case reports of Huntington disease that were confirmed at autopsy, but to our knowledge, there are no reports in the literature where the diagnosis of Huntington disease was first made at autopsy. We present a case of a 28-year-old African-American male who was in a state of neglect due to a lifetime of abuse, cognitive difficulties, and seizures, whose cause of death was pneumonia. The gross autopsy findings included bilateral caudate nucleus atrophy and lateral ventricular dilation. Microscopically, severe bilateral neuronal loss and gliosis of the caudate and putamen nuclei were seen. Genetic testing for the number of CAG repeats confirmed the diagnosis and was consistent with JHD.

Dysregulation of Toll-Like Receptor 7 Compromises Innate and Adaptive T Cell Responses and Host Resistance to an Attenuated West Nile Virus Infection in Old Mice.

UNLABELLED: The elderly are known to have enhanced susceptibility to infections and an impaired capacity to respond to vaccination. West Nile virus (WNV), a mosquito-borne flavivirus, has induced severe neurological symptoms, mostly in the elderly population. No vaccines are available for human use. Recent work showed that an attenuated WNV, a nonstructural (NS) 4B-P38G mutant, induced no lethality but strong immune responses in young (6- to 10-week-old) mice. While studying protective efficacy, we found unexpectedly that old (21- to 22-month) mice were susceptible to WNV NS4B-P38G mutant infection but were protected from subsequent lethal wild-type WNV challenge. Compared to responses in young mice, the NS4B-P38G mutant triggered higher inflammatory cytokine and interleukin-10 (IL-10) production, a delayed γδ T cell expansion, and lower antibody and WNV-specific T cell responses in old mice. Toll-like receptor 7 (TLR7) is expressed on multiple types of cells. Impaired TLR7 signaling in old mice led to dendritic cell (DC) antigen-presenting function compromise and a reduced γδ T cell and regulatory T cell (Treg) expansion during NS4B-P38G mutant infection. R848, a TLR7 agonist, decreased host vulnerability in NS4B-P38G-infected old mice by enhancing γδ T cell and Treg expansion and the antigen-presenting capacity of DCs, thereby promoting T cell responses. In summary, our results suggest that dysregulation of TLR7 partially contributes to impaired innate and adaptive T cell responses and an enhanced vulnerability in old mice during WNV NS4B-P38G mutant infection. R848 increases the safety and efficacy during immunization of old mice with the WNV NS4B-P38G mutant. IMPORTANCE: The elderly are known to have enhanced susceptibility to infections and an impaired capacity to respond to vaccination. West Nile virus (WNV), an emerging mosquito-borne flavivirus, has induced severe neurological symptoms more frequently in the elderly population. No vaccines are available for human use. Here, we used an aged mouse model to investigate the protective efficacy of an attenuated WNV, the nonstructural 4B-P38G mutant, which was previously shown to induce no lethality but strong immune responses in young adult mice. Studies that contribute to a mechanistic understanding of immune defects in the elderly will allow the development of strategies to improve responses to infectious diseases and to increase vaccine efficacy and safety in aging individuals.

Characterization of lethal dengue virus type 4 (DENV-4) TVP-376 infection in mice lacking both IFN-α/ß and IFN-γ receptors (AG129) and comparison with the DENV-2 AG129 mouse model.

Dengue is a mosquito-borne disease caused by four related but distinct dengue viruses, DENV-1 to DENV-4. Dengue is endemic in most tropical countries, and over a third of the world's population is at risk of being infected. Although the global burden is high, no vaccine or antiviral is licensed to combat this disease. An obstacle complicating dengue research is the lack of animal challenge models that mimic human disease. Advances in immunocompromised murine infection models resulted in development of lethal DENV-2, DENV-3 and DENV-4 models in AG129 mice, which are deficient in both the IFN-α/ß receptor (IFN-α/ßR) and the IFN-γ receptor (IFN-γR). These models mimic features of dengue disease in humans. Here, we characterized lethal infection of AG129 mice by DENV-4 strain TVP-376 and found that AG129 mice developed clinical signs of illness and high viral loads in multiple tissues and succumbed 5 days after infection. Moreover, the splenic and hepatic histopathology of TVP-376-infected mice demonstrated the presence of cell activation and destruction of tissue architecture. Furthermore, infected mice had heightened levels of circulating cytokines. Comparison of the virulence phenotypes of DENV-4 strain TVP-376 and DENV-2 strain D2S10 revealed that TVP-376-induced mortality occurred in the absence of both IFN-α/ßR and IFN-γR signalling, but not with intact signalling from the IFN-γR, whereas D2S10 required the absence of IFN-α/ßR signalling only, indicating that it is more virulent than TVP-376. In conclusion, TVP-376 is lethal in AG129 mice, and this model provides a useful platform to investigate vaccine candidates and antivirals against DENV-4.

A Dengue Virus Type 4 Model of Disseminated Lethal Infection in AG129 Mice.

Dengue is a mosquito-borne disease of global public health significance that is caused by four serologically and genetically related viruses (DENV-1 to DENV-4). Most human DENV infections are asymptomatic, but clinical cases can range in severity from a relatively mild self-limiting illness to a severe life-threatening disease. Infection with one serotype of DENV results in life-long homotypic immunity but only short term heterotypic protection. There are no licensed vaccines or antivirals for dengue due in part to difficulty in developing small animal models that mimic the systemic disease seen in humans. Consequently, an important advance was the description of models of DENV-2 infection in AG129 mice (deficient in interferon alpha/beta and gamma receptor signaling) that resemble human disease. However, the need for well characterized models of disease due to DENV-1, -3, and -4 still remains. Here we describe a new AG129 mouse model utilizing a non-mouse-adapted Thai human DENV-4 strain 703-4. Following intraperitoneal challenge, animals experience a rapidly progressive lethal infection without developing neurologic clinical signs of disease. High virus titers are seen in multiple visceral tissues including the liver, spleen and large intestine, and the infected animals develop vascular leakage and thrombocytopenia, hallmarks of human dengue. Taken together, our studies demonstrate that this model is an important addition to the field of dengue research particularly in understanding similarities and differences in the pathologic basis of the disease caused by different DENV serotypes and in determining comparative efficacy of putative vaccines and antivirals.

A lethal murine infection model for dengue virus 3 in AG129 mice deficient in type I and II interferon receptors leads to systemic disease.

UNLABELLED: The mosquito-borne disease dengue (DEN) is caused by four serologically and genetically related viruses, termed DENV-1 to DENV-4. Infection with one DENV usually leads to acute illness and results in lifelong homotypic immunity, but individuals remain susceptible to infection by the other three DENVs. The lack of a small-animal model that mimics systemic DEN disease without neurovirulence has been an obstacle, but DENV-2 models that resemble human disease have been recently developed in AG129 mice (deficient in interferon alpha/beta and interferon gamma receptor signaling). However, comparable DENV-1, -3, and -4 models have not been developed. We utilized a non-mouse-adapted DENV-3 Thai human isolate to develop a lethal infection model in AG129 mice. Intraperitoneal inoculation of six to eight-week-old animals with strain C0360/94 led to rapid, fatal disease. Lethal C0360/94 infection resulted in physical signs of illness, high viral loads in the spleen, liver, and large intestine, histological changes in the liver and spleen tissues, and increased serum cytokine levels. Importantly, the animals developed vascular leakage, thrombocytopenia, and leukopenia. Overall, we have developed a lethal DENV-3 murine infection model, with no evidence of neurotropic disease based on a non-mouse-adapted human isolate, which can be used to investigate DEN pathogenesis and to evaluate candidate vaccines and antivirals. This suggests that murine models utilizing non-mouse-adapted isolates can be obtained for all four DENVs. IMPORTANCE: Dengue (DEN) is a mosquito-borne disease caused by four DENV serotypes (DENV-1, -2, -3, and -4) that have no treatments or vaccines. Primary infection with one DENV usually leads to acute illness followed by lifelong homotypic immunity, but susceptibility to infection by the other three DENVs remains. Therefore, a vaccine needs to protect from all four DENVs simultaneously. To date a suitable animal model to mimic systemic human illness exists only for DENV-2 in immunocompromised mice using passaged viruses; however, models are still needed for the remaining serotypes. This study describes establishment of a lethal systemic DENV-3 infection model with a human isolate in immunocompromised mice and is the first report of lethal infection by a nonadapted clinical DENV isolate without evidence of neurological disease. Our DENV-3 model provides a relevant platform to test DEN vaccines and antivirals.

Evidence for autophagic gridlock in aging and neurodegeneration.

Autophagy is essential to neuronal homeostasis, and its impairment is implicated in the development of neurodegenerative pathology. However, the underlying mechanisms and consequences of this phenomenon remain a matter of conjecture. We show that misexpression of human tau in Drosophila induces accumulation of autophagic intermediates with a preponderance of large vacuoles, which we term giant autophagic bodies (GABs), which are reminiscent of dysfunctional autophagic entities. Lowering basal autophagy reduces GABs, whereas increasing autophagy decreases mature autolysosomes. Induction of autophagy is also associated with rescue of the tauopathy phenotype, suggesting that formation of GABs may be a compensatory mechanism rather than a trigger of neurodegeneration. Last, we show that the peculiar Biondi bodies observed in the choroid epithelium of both elderly and Alzheimer's disease human brains express immunoreactive markers similar to those of GABs. Collectively, these data indicate that autophagic gridlock contributes to the development of pathology in aging and neurodegeneration.

Should high-risk adolescents have Papanicolaou tests?

BACKGROUND: The current American College of Obstetricians and Gynecologists guidelines state that cervical cancer screening should begin at age 21 years, regardless of sexual or obstetric history. However, previous studies have demonstrated that there is a small but significant subset of high-risk adolescents with extensive sexual and obstetric history who harbor a significant squamous cervical lesion. The objective of the current study was to use histologic and demographic data from adolescents (aged <21 years) who received Papanicolaou (Pap) tests to determine whether they benefited from early cervical cancer screening. METHODS: Adolescent girls who had Pap tests between 2000 and 2010 were included in the study. Demographic data, including obstetric history, number of sexual partners, age of first coitus, age at first pregnancy, menarche, smoking history, and Chlamydia and syphilis infection, were analyzed for associations with levels of cervical dysplasia. RESULTS: Of 56,785 adolescent Pap tests, 277 (0.5%) were diagnosed as high-grade squamous HSIL, and 56 of those Pap tests (20%) were from patients who had grade 3 cervical intraepithelial neoplasia (CIN-3) on subsequent biopsy and/or excision. One patient had microinvasive cervical carcinoma identified on loop electrosurgical excision procedure at age 27 years after an HSIL Pap test. Increased parity was associated significantly with higher rates of CIN-3. CONCLUSIONS: The study findings indicated that current American College of Obstetricians and Gynecologists guidelines to begin Pap testing at age 21 years are appropriate for the majority of adolescents, because the rate of HSIL is very low, and the risk for invasive carcinoma is minimal. Although higher parity was associated with a significantly increased grade of CIN, the conclusions are questionable because of the significant amount of missing demographic data points. That being said, this study should lead to other similar studies to determine any association of higher grade CIN with adolescent sexual and obstetric history.