Biomedical subjects

Michele Follen

Publications and source records attributed to Michele Follen.

At least 19 recordsLinked to original sources

PubMed2005

Sources of scattering in cervical tissue: determination of the scattering coefficient by confocal microscopy.

Most models of light propagation through tissue assume that the scattering properties of various tissue layers are the same. We present evidence that the scattering coefficient of cervical epithelium varies by a factor of 3 within the epithelium owing to variations in nuclear density and to the presence of keratin. We estimated the scattering coefficient from regions of normal and precancerous cervical epithelium by fitting reflectance measurements from confocal images to an exponential function of depth based on Beer's law of attenuation. The results suggest that the normal cervix is characterized by highly variable scattering in the superficial epithelium, low scattering in the intermediate epithelium, and high scattering in the basal and stromal regions. In high-grade dysplasia, high scattering from high-density nuclei is observed throughout the entire epithelium.

Algorithms↗

PubMed2005

In vivo fiber-optic confocal reflectance microscope with an injection-molded plastic miniature objective lens.

For in vivo optical diagnostic technologies to be distributed to the developed and developing worlds, optical imaging systems must be constructed of inexpensive components. We present a fiber-optic confocal reflectance microscope with a cost-effective injection-molded plastic miniature objective lens for in vivo imaging of human tissues in near real time. The measured lateral resolution is less than 2.2 microm, and the measured axial resolution is 10 microm. Confocal images of ex vivo cervical tissue biopsies and in vivo human lip taken at 15 frames/s demonstrate the microscope's capability of imaging cell morphology and tissue architecture.

Cervix Uteri↗

PubMed2005

Results of a phase II double-blinded randomized clinical trial of difluoromethylornithine for cervical intraepithelial neoplasia grades 2 to 3.

PURPOSE: Our purpose was to conduct a double-blinded randomized trial of difluoromethylornithine (DFMO) at 0.125, 0.5 gm/m2, versus placebo in the treatment of cervical intraepithelial neoplasia (CIN) grades 2 to 3. A promising phase I study has shown histopathologic responses at these dose levels. EXPERIMENTAL DESIGN: Patients with histopathologically confirmed CIN 2-3 lesions were recruited from a colposcopy clinic and underwent Papanicolaou testing, human papillomavirus testing, and colpophotography. They took oral contraception and DFMO or placebo elixir for 28 days and filled out the National Cancer Institute common toxicity calendars. They returned for follow-up and a repeat Papanicolaou smear, colpophotograph, and loop excision of the cervix. RESULTS: There were no statistically significant differences among the arms in histopathologic response. This could no be explained by any biases in risk factors. The prominent toxicities were diarrhea, dizziness, nausea, and headaches. There were no differences in the toxicities among arms. The Papanicolaou smear was a poor biomarker of response and correlated poorly with the histopathology. CONCLUSIONS: DFMO is no active at 0.125 and 0.5 gm/m2 for 28 days when given orally in CIN 2-3. Higher oral doses or longer administration is necessary, supporting data from breast trials. Alternatively, a trial of topical DFMO might merit attention as activity has been noted in trials of actinic keratoses.

Adolescent↗

PubMed2005

Human papillomavirus type 16 E2 and E6/E7 variants.

OBJECTIVES: Polymorphisms in human papillomavirus (HPV) type 16 have been shown to be related to geographic areas and are broadly classified as European (E), African (Af), Asian (As), or Asian-American (AA). Certain variants have been reported as being more likely to cause cervical disease; our objectives were to identify new HPV16 polymorphisms, to determine the linkage of the E2 and E6/E7 regions and to determine the minimum sequence necessary to classify variants. METHODS: We sequenced the complete E2, E6, and E7 regions in all HPV16-positive cervical samples identified in a case-control study of pre-invasive cervical disease. RESULTS: In the 100 samples analyzed, only one new polymorphism was identified, a synonymous change, T3205A, in region E2. The frequency distribution of variants in the sample set was 37 European prototypes and 27 E-G350, 16 AA, 5 Af1, 2 Af2, 8 E-C109G, 3 E-G131G, and 2 As. As shown by others, region E7 varied much less than E6 and E2. CONCLUSIONS: In each case, E2 changes were linked to the expected E6/E7 changes, and there was no evidence for recombination. The linkage between E2 and E6/E7 allows variant classification to be based on a short E6 sequence (nt 109-350).

Base Sequence↗

PubMed2005

See-and-treat strategy for diagnosis and management of cervical squamous intraepithelial lesions.

In a see-and-treat protocol, patients referred for colposcopy because of an abnormal Pap smear in cervical-cancer screening can be treated by loop excision, without biopsy, during one visit to the clinic. However, overtreatment in the see-and-treat strategy has been reported to be 1.2-83.3% for low-grade squamous intraepithelial lesions (SIL) and to be 13.3-83.3% for high-grade SIL. Range of overtreatment narrowed to 4.0-23.5% for those with normal pathology and to 18.0-29.4% for those with normal or low-grade pathology when calculation of overtreatment was restricted to patients diagnosed with high-grade SIL on colposcopy and referral Pap smear. Most common treatment complications are bleeding and infection. Nonetheless, the strategy has become accepted internationally: low costs, decreased patient anxiety, and increased compliance make it appealing, especially in settings with limited health resources, and for patients at risk of not being treated in a timely manner or of not returning for a second appointment. Mathematical modelling may give information about the appropriateness and usefulness of this treatment while the results of long-term clinical trials are awaited.

Clinical Trials as Topic↗

PubMed2004

Exploratory analysis of quantitative histopathology of cervical intraepithelial neoplasia: objectivity, reproducibility, malignancy-associated changes, and human papillomavirus.

BACKGROUND: As part of a project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analyses of biopsy specimens from 1,190 patients. Objectives in the interim analysis are (a) quantitatively assessing progression of the neoplastic process of cervical intraepithelial neoplasia (CIN)/squamous intraepithelial lesions (SIL), (b) detecting malignancy-associated changes (MACs), and (c) phenotypically measuring human papillomavirus (HPV) detected by DNA testing. METHODS: The diagnostic region of interest (ROI) from immediately adjacent sections were imaged, and the basal lamina and surface of the superficial layer were delimited. Nonoverlapping quantitatively stained nuclei were selected from 1,190 samples with histopathological characteristics of normal (929), koilocytosis (130), CIN 1 (40), CIN 2 (23), and CIN 3/carcinoma in situ (CIS) (68). A fully automatic procedure located and recorded the center of every nucleus in the region of interest (ROI). We used linear discriminant analysis to assess the changes between normal and CIN 3/CIS. RESULTS: Scores computed from the cell-by cell features and the clinical grade of CIN/SIL were highly correlated, as were those of the architectural features and the clinical grade of CIN/SIL. We found even higher correlations between a combination of cell-by-cell and architectural scores, and clinical grade. Using these scores, we found MACs in the normal biopsy specimens from patients with high-grade CIN/SIL. Furthermore, the same scores correlated with the molecular detection of HPV. CONCLUSIONS: Quantitative histopathology can be used in large clinical trials as an objective and reproducible measure of CIN/SIL. Detectable phenotypic changes correlate well with CIN/SIL neoplastic progression. It can also be used to infer the presence of CIN/SIL (MACs) and molecular changes associated with increased risk of cancer development (high-risk HPV).

DNA, Viral↗

PubMed2004

The effects of repeated spectroscopic pressure measurements on fluorescence intensity in the cervix.

OBJECTIVE: Fluorescence spectroscopy is a promising technology for the detection of cervical squamous intraepithelial lesions (SILs). In this study we took repeated measures in the cervix to determine whether the order of measurement produces changes in fluorescence intensity and whether there are differences in variation due to pressure. METHODS: A pressure sensitive fiber-optic probe to measure fluorescence spectra was calibrated at light, medium, and firm levels (0.2, 0.4, 0.6 N). Measurements were made 3 times at each of 2 sites in the patient's cervix. Spectroscopic data were preprocessed and analyzed to compare order of pressure and intensity variability as a function of pressure on measurements. RESULTS: Four providers took 3 measurements from 2 sites each in 18 patients, yielding 108 measurements. After corrections for multiple comparisons, neither the order of probe pressure nor the variability of probe pressure significantly affected variations in fluorescence intensity. CONCLUSION: This study shows that the probe pressure variability is probably not an issue for these devices.

Adult↗

PubMed2004

Quantitative histopathology and chromosome 9 polysomy in a clinical trial of 4-HPR.

OBJECTIVE: This trial examined the use of 4-hydroxyphenyl-retinamide (4-HPR), demonstrated to be a potent inhibitor of carcinogenesis in vitro and in animal models, in patients with cervical intraepithelial neoplasia (CIN) grades 2 to 3. Quantitative pathology and chromosome 9 polysomy were used to understand the biology and quantify the clinical histopathologic changes observed. METHODS: Patients were randomized to 4-HPR or placebo for 6 months and followed for six more months. Cervical biopsies were obtained at baseline, 6 months, and 12 months; the biopsies were read blinded three times by the study pathologist. Feulgen-stained sections were also obtained and analyzed using computer-assisted image cytometry. Chromosome 9 polysomy was performed on tissue slices using in situ hybridization and measured quantitatively. Statistical analyses were carried out in S-Plus (Insightful Corporation, Seattle, WA) and R. RESULTS: The interim analysis, planned for 40 patients, was carried out on 39. The 6- and 12-month analyses showed a statistically significant difference between the two study arms. When code was broken, the 4-HPR-treatment arm was found to have fared less well than placebo. Analyses of Feulgen-stained sections provided a quantitative measure of the increase of DNA content and texture features. Chromosome 9 polysomy was also measured using image analysis. The changes observed were consistent with those of cells displaying cancerous changes, indicating a lack of response. CONCLUSION: 4-HPR is not active at 200 mg/day. The interim analysis was helpful in directing the study; and, in this case, ending it. The intermediate endpoint biomarkers of quantitative histomorphometry and chromosome 9 polysomy yielded quantitative and repeatable results consistent with the findings of the clinical pathologist.

Anticarcinogenic Agents↗

PubMed2004

Distress after an abnormal Pap smear result: scale development and psychometric validation.

BACKGROUND: Psychological distress is severe in women who receive a report of abnormal findings on Pap smear, and may be one reason 10-61% of such women fail to undergo follow-up testing. METHODS: Using the 14-question Psychosocial Effects of Abnormal Pap Smears Questionnaire (PEAPS-Q) as a basis, we developed the 23-question Cervical Dysplasia Distress Questionnaire (CDDQ), testing its internal consistency and validity with 661 women undergoing colposcopy after an abnormal Pap smear finding in a three-phase analysis. RESULTS: Items were divided into two sets and factor analyzed separately: one addressed distress during medical procedures, and the other concerned perceived consequences of an abnormal Pap smear. The medical procedures items yielded two factors: embarrassment regarding the procedures and discomfort/tension with the procedures. Factor analysis of the second set also resulted in two factors: concern about sexual and reproductive issues and concern about health consequences. Subscales created from items loading highly on each factor had high internal consistency (alpha ranged from 0.76 to 0.90) and demonstrated good concurrent validity with other psychometrically validated measures of distress. CONCLUSIONS: The CDDQ is a reliable and valid questionnaire for measuring multiple domains of distress unique to women who test positive on a cervical cancer screening test.

Adult↗

PubMed2004

Depressed type 1 cytokine synthesis by superantigen-activated CD4+ T cells of women with human papillomavirus-related high-grade squamous intraepithelial lesions.

Carcinoma of the cervix is causally related to infection with the human papillomavirus (HPV), and T cells play a pivotal role in the immune response of the host to rid itself of HPV infection. Therefore, we assessed the T-cell function of women with HPV-related cervical neoplasia against a superantigen, Staphylococcus enterotoxin B (SEB). Each woman provided a cervical brush specimen for HPV DNA testing and Papanicolaou (Pap) smears for the staging of cervical lesions. They also provided a blood specimen for determination of the ability of CD4(+) T and CD8(+) T cells to synthesize Th1 (interleukin-2 [IL-2], gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) and Th2 (IL-10) cytokines in response to activation with SEB. Compared with control subjects with self-attested negative Pap smears, women with high-grade squamous intraepithelial lesions (HSIL) had significantly lower percentages of activated CD4(+) T cells that produced IL-2 (P = 0.045), IFN-gamma (P = 0.040), and TNF-alpha (P = 0.015) and a significantly lower percentage of activated CD8(+) T cells that produced IL-2 (P < 0.01). These data indicate that women with HPV-related cervical HSIL show a decrease in Th1 cytokine production by activated CD4(+) T cells and suggested that compromised T-helper functions may negatively impact the function of cytotoxic CD8(+) T cells.

Antigens, Bacterial↗

PubMed2004

Quantitative histopathological analysis of cervical intra-epithelial neoplasia sections: methodological issues.

OBJECTIVES: As part a Program Project to evaluate emerging optical technologies for cervical neoplasia, our group is performing quantitative histopathological analysis of biopsies from 1,800 patients. Several methodological issues have arisen with respect to this analysis: (1) Finding the most efficient way to compensate for staining intensity variation with out losing diagnostic information; (2) Assessing the inter- and intra-observer variability of the semi-interactive data collection; and (3) the use of non-overlapping cells from the intermediate layer only. METHODS: Non-overlapping quantitatively stained nuclei were selected from 280 samples with histopathological characteristics of normal (199), koilocytosis (37), CIN 1 (18), CIN 2 (10) and CIN 3 (16). Linear discriminant analysis was used to assess the diagnostic information in three different feature sets to evaluate and compare staining intensity normalization methods. Selected feature values and summary scores were used to evaluate intra- and inter-observer variability. RESULTS: The features normalized by the internal subset of the imaged cells had the same discriminatory power as those normalized by the control cells and by both normalization methods seem to have additional discriminatory power over the set of features which do not require normalization. The use of the internal subset decreased the image acquisition time by approximately 50% at each center, respectively. The intra- and inter-observer variability was of a similar size. Good performance was obtained by measuring the intermediate layer only. CONCLUSION: The use of intensity normalization from a subset of the imaged non-overlapping intermediate layer cells works as well as or better than any of the other methods tested and provides a significant timesaving. Our intra- and inter-observer variability do not seem to affect the diagnostic power of the data. Although this must be tested in a larger data set, the use of intermediate layer cells only may be acceptable when using quantitative histopathology.

Cell Nucleus↗

PubMed2004

Quality assurance system using statistical process control: an implementation for image cytometry.

AIMS: Optical technologies have shown some promise for improving the care of cervical neoplasia. We are currently evaluating fluorescence and reflectance spectroscopy and quantitative cyto-histopathology for cervical neoplasia screening and diagnosis. Here we describe the establishment and application of a quality assurance (QA) system for detecting system malfunctions and assessing the comparability of four image cytometers used in a multicenter clinical trial. METHODS: Our QA system involves three levels of evaluation based on the periodicity and complexity of the measurements. We implemented our QA system at three image cytometers at the British Columbia Cancer Agency and one at M.D. Anderson Cancer Center. The measurements or tasks were performed daily, monthly, and semi-annually. The current and voltage of the lamp, the calibration image characteristics, and the room temperature were checked daily. Long-term stability over time, short-term variability over time, and spatial response field uniformity were evaluated monthly. Camera linearity was measured semi-annually. Control charts based on statistical process control techniques were used to detect when the system did not perform optimally. RESULTS: Daily measurements have shown good consistency in room temperature, lamp and calibration behaviour. Monthly measurements have shown small coefficients of variation between and within the four devices. There have been greater differences between sessions than within sessions. Comparability among the four systems is reasonably good. Semi-annual measurements have shown stable camera linearity. QA events were detected using the QA system. Multiple examples of event detection leading to correction of system malfunction are described in this report. CONCLUSIONS: QA programs are critical for ensuring data integrity and therefore for the conduct of multicenter clinical trials.

Female↗

PubMed2003

Cervical cancer chemoprevention, vaccines, and surrogate endpoint biomarkers.

At the Second International Conference on Cervical Cancer, held April 11-14, 2002, experts in cervical cancer prevention, detection, and treatment reviewed the need for more research in chemoprevention, including prophylactic and therapeutic vaccines, immunomodulators, peptides, and surrogate endpoint biomarkers. Investigators and clinicians noted the need for more rigorous Phase I randomized clinical trials, more attention to the risk factors that can affect study results in this patient population, and validation of optical technologies that will provide valuable quantitative information in real time regarding disease regression and progression. They discussed the role of the human papillomavirus (HPV) in cervical cancer development and the importance of developing strategies to suppress HPV persistence and progression. Results in Phase I randomized clinical trials have been disappointing because few have demonstrated statistically significant regression attributable to the agent tested. Researchers recommended using a transgenic mouse model to test and validate new compounds, initiating vaccine and immunomodulator trials, and developing immunologic surrogate endpoint biomarkers.

Biomarkers, Tumor↗

PubMed2003

Optical imaging of the cervix.

Recent advances in fiber optics, sources and detectors, imaging, and computer-controlled instrumentation have stimulated a period of unprecedented growth in the development of photonics technologies for a wide variety of diagnostic and therapeutic clinical applications. These include the application of quantitative optical spectroscopy and imaging for the detection of precancerous lesions in the uterine cervix, a topic of interest at the Second International Conference on Cervical Cancer, which was held April 11-14, 2002. Investigators have applied the Littenberg method of emerging technology assessment to new optical methods used to detect cervical neoplasia. Currently, such technologies as fluorescence spectroscopy (the combination of fluorescence and diffuse reflectance spectroscopy), tri-modal spectroscopy, and light-scattering spectroscopy that probe the spectral characteristics of tissue are being investigated. Optical technologies that create images of subcellular structure without biopsy subsequent to pathology that currently are under investigation include in vivo confocal imaging and optical coherence tomography. Numerous small studies have demonstrated the potential of these optical technologies. What remains to be elucidated are the fundamental biophysical origins of variations in remitted optical signals between normal and dysplastic tissue. Large multicenter randomized controlled trials are needed to confirm the detection and imaging capabilities of optical technology. Furthermore, the development of contrast agents that could boost detection with these technologies is needed, and basic biologic characterization of signals should be pursued. Applying the Littenberg assessment will help ensure that superior, not simply alternative, technologies are implemented.

Cervix Uteri↗

PubMed2003

Imaging in cervical cancer.

Cervical cancer traditionally has been staged clinically. Advances in imaging could improve the staging of cervical cancer by facilitating the detection of lymph node metastases and micrometastases in distant organs. Such progress could lead to improvements in treatment selection and therefore increase overall survival rates. At the Second International Conference on Clinical Cancer (Houston, TX, April 11-14, 2002), a panel composed of gynecologic oncologists, radiation oncologists, and diagnostic radiologists reviewed relevant technologies. Advances in lymphangiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), and lymphatic mapping were reviewed, along with the impact of these advances on the diagnosis, treatment, and survival of patients with cervical cancer. Few cancer centers still use lymphangiography, but the sensitivity of this method ranges from 28% to 83%, with specificity ranging from 47% to 100%. The roles of transabdominal and transvaginal ultrasonography in evaluating cervical cancer are expected to expand when new contrast agents increase the sensitivity of these techniques to parametrial invasion and lymph node metastases; meanwhile, ultrasonography's most significant contributions may involve the identification of uterine and cervical leiomyomas and the evaluation of urinary tract obstruction. Advances in CT have made it a rival technique to MRI, but limitations prevent CT from providing definitive information on certain parameters. MRI, which is valuable because of its superior soft tissue contrast resolution, multiplanar capabilities, and cost-effectiveness, is used to determine the size of the cervix and to detect certain types of invasion, characteristics of lymph nodes, and the presence of disease in the ureter, lung, and liver. PET with 2-[fluorine-18]fluoro-2-deoxy-D-glucose has been found to detect abnormal lymph node regions better than CT does but PET can also be used in conjunction with CT to measure tumor dimensions. PET also has become a method for identifying tumors that are unresponsive to chemoradiation. When used together with immunohistochemical and molecular techniques as well as conventional stains, sentinel lymph node mapping, an important development in the surgical management of solid tumors, is expected to improve gynecologic cancer management. Advances in imaging methods and in contrast agents, along with advances in the combined use of the two, are expected to make imaging technologies more valuable in cervical cancer assessment.

Diagnostic Imaging↗

PubMed2003

Serum levels of insulin-like growth factor I and risk of squamous intraepithelial lesions of the cervix.

Squamous intraepithelial lesions (SILs) are areas of precancerous growth in the cervix that can be indicative of future cervical cancer. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) have been implicated in cancer development. Recent studies have demonstrated that elevated plasma IGF-I levels are associated with increased risk of prostate, lung, colon, and breast cancers. In this case-control study, we analyzed the relationship between serum levels of IGF-I and IGFBP-3, and SILs of the cervix. The case patients were comprised of 267 women treated at The University of Texas M. D. Anderson Cancer Center Colposcopy Clinic in Houston, Texas for abnormal Pap smears. The clinic serves minority and economically disadvantaged women referred from the County Health Department clinics of Harris County, Texas. The control subjects were 238 healthy women receiving family planning and screening services at two Harris County Health Department clinics. Case patients with either high-grade or low-grade SILs had significantly higher serum levels of IGF-I, IGFBP-3, and molar ratios of IGF-I:IGFBP-3 than the control subjects did. IGF-I levels in the highest quartile were associated with significantly higher risk of SILs compared with the lowest quartile, independent of IGFBP-3 levels. The odds ratio for the fourth quartile of IGF-I level, relative to the first quartile, was 8.54 (95% confidence interval, 4.15-17.60; P < 0.0001) after adjustment for age, ethnicity, smoking status, and IGFBP-3 level. There was a dose-response relationship between risk of SILs and the level of IGF-I: as the level of IGF-I increased, so did the risk of SILs. In addition, the serum level of IGFBP-3 was significantly higher in case patients than in control subjects. However, after adjustment for IGF-I, no relationship was evident between IGFBP-3 level and risk of SILs. Serum levels of IGF-I may be a useful biomarker for assessing risk of SIL development.

Adult↗

PubMed2003

Real-time vital optical imaging of precancer using anti-epidermal growth factor receptor antibodies conjugated to gold nanoparticles.

Recent developments in photonic technology provide the ability to noninvasively image cells in vivo; these new cellular imaging technologies have the potential to dramatically improve the prevention, detection, and therapy of epithelial cancers. Endoscope-compatible microscopies, such as optical coherence tomography and reflectance confocal microscopy, image reflected light, providing a three-dimensional picture of tissue microanatomy with excellent spatial resolution (1-10 micro m). However, their ability to image molecular biomarkers associated with cancer is limited. Here, we describe a new class of molecular specific contrast agents for vital reflectance imaging based on gold nanoparticles attached to probe molecules with high affinity for specific cellular biomarkers. The application of gold bioconjugates for vital imaging of precancers is demonstrated using cancer cell suspensions, three-dimensional cell cultures, and normal and neoplastic fresh cervical biopsies. We show that gold conjugates can be delivered topically for imaging throughout the whole epithelium. These contrast agents have potential to extend the ability of vital reflectance microscopies for in vivo molecular imaging. They can potentially enable combined screening, detection, and therapy of disease using inexpensive imaging systems; such tools could allow mass screening of diseases such as cancer in resource-poor settings.

Antibodies, Monoclonal↗

PubMed2003

Lymphangioma circumscriptum of the vulva: a review of the literature.

OBJECTIVE: To promote proper identification and management of this rare entity by presenting a review of the literature, a case report, and illustrations of its presentation and pathology. DATA SOURCES: Sources searched included the literature contained in the National Library of Medicine's PubMed database, using the term "lymphangioma circumscriptum" combined with "vulva." Other search terms used were "capillary lymphangioma," "lymphangiectasia," and "dermal lymphangioma." Sources also included articles predating the PubMed database that were cited by other writers. METHODS OF STUDY SELECTION: Selections were restricted to the English-language medical literature published since 1960, and the search resulted in retrieval of 3272 published papers about lymphangioma. TABULATION, INTEGRATION, AND RESULTS: Congenital lymphangioma circumscriptum of the vulva has been reported in 11 patients, including one case reported and illustrated in this paper, and acquired lymphangioma circumscriptum has been reported in 20. It affects females 9-76 years old (mean 42.5 years). Clinically, it is characterized by persistent clusters of thin-walled vesicles filled with clear fluid. The diagnosis is usually made by biopsy, as these lesions often mimic such infectious diseases as molluscum contagiosum. Management options have included surgical excision of the skin and subcutaneous tissue, surface abrasion by laser or sclerosing therapy, and observation. CONCLUSION: From this comprehensive review, which includes the clinicopathologic features of both the congenital and acquired forms, illustrations from the rarest form, and a summary of treatment approaches, we conclude that lymphangioma circumscriptum poses a diagnostic challenge the risks of which are misdiagnosis and mistreatment. These risks would likely be reduced were a database of cases accessible that permitted long-term follow-up and better assessment of presenting characteristics and treatment options.

Adult↗