Testing Algorithms for the Diagnosis of Malignant Glandular Tumors of the Uterine Cervix Histotyped per the International Endocervical Adenocarcinoma Criteria and Classification (IECC) System.

The International Endocervical adenocarcinoma Criteria and Classification (IECC) categorizes tumors into human papilloma virus (HPV) associated (HPVA), not associated (NHPV), and invasive adenocarcinoma not otherwise specified (IA NOS). HPVA and NHPV encompass 11 histotypes and an algorithm of mucin content, HPV ribonucleic acid (RNA), estrogen receptor and GATA3 is proposed for the diagnosis of most. In this study, the IECC algorithm's diagnoses were compared with hematoxylin and eosin (H&E) based IECC histotyping. Kappa statistics measured performance agreement. With additional markers, hierarchical clustering by random forest (RF) classification identified the most discriminating between tumor types, and investigated other algorithms. Three pathologists independently reviewed digitized H&E images of n=152 primary cervical adenocarcinomas for IECC histotype and mucin content, and tissue microarrays for expression of HPV RNA by in situ hybridization and 16 antibodies by immunohistochemistry. Results were finalized by consensus. There were n=113 HPVA, n=22 NHPV, and n=17 IA NOS. Mucin was obvious in n=36 and limited in n=116. Among n=124 with satisfactory test results, HPV RNA was positive in n=96, estrogen receptor in n=72, and GATA3 in n=15. The IECC algorithm diagnosed n=99 which agreed with H&E histotyping in n=64 for a fair κ of 0.36 (95% confidence interval, 0.21-0.50): n=12 were undiagnosed and n=13 were IA NOS. Small sample sizes restricted RF to HPVA versus NHPV which were discriminated by p16, HPV RNA, and MUC6 with an area under the curve of 0.74 (95% confidence interval, 0.58-0.90). The IECC algorithm for histotyping under-performed. The RF algorithmin for categorization was favorable, but validation in larger studies and investigation of additional algorithms to discriminate between all IECC histotypes are needed.

Adenocarcinoma of the Uterine Cervix: Immunohistochemical Biomarker Expression and Diagnostic Performance.

Immunohistochemistry (IHC) improves the diagnosis of cervical adenocarcinoma but is not adequately studied. The performance of 16 antibodies previously reported as potentially discriminating between some histotypes was investigated in 184 tumors comprised of 12 histotype groups collapsed into 3 categories [47 adenocarcinomas in situ (AIS), 121 probable human papillomavirus-dependent adenocarcinomas (HPVD), and 16 of probable independence (HPVI)]. IHC sections from 5 tissue microarrays were scanned, and 3 pathologists independently reviewed images to assess staining percentages and intensities. Biomarker expression was based on published positive and negative cutoffs and agreement between any 2 pathologists. Differences between the 3 categories in the hierarchical ranking of biomarker positivity were analyzed by Random Forest classification, and between select groups by Unsupervised Hierarchical Clustering. Important category discriminants were combined in logistic regression models and the area under the curve (AUC) computed. Potential group discriminants were terminal cluster biomarkers with a 50% or more difference in positivity. Strong associations occurred between the lower expression of carcinoembryonic antigen and stromal actin in AIS compared with HPVD [AUC=0.70, 95% confidence interval (CI), 0.59-0.80] and in the higher expression of p16 and estrogen receptor in comparison to HPVI (AUC=0.86, 95% CI, 0.73-0.98), and between the higher expression of p16, carcinoembryonic antigen and estrogen receptor in HPVD compared with HPVI (AUC=0.88, 95% CI, 0.77-0.99). Between select groups, 9 biomarkers emerged as potential discriminants. Select IHC biomarkers can discriminate AIS from invasive adenocarcinomas, and invasive adenocarcinomas stratified by human papillomavirus dependency from each other. Independent replication in larger studies is needed, and to confirm discriminants of histotype groups.

FIGO Stage Is the Strongest Prognostic Factor in Adenocarcinoma of the Uterine Cervix.

OBJECTIVE: This study aimed to identify clinical and pathological determinants of invasive adenocarcinoma of the uterine cervix (AC) in a large, single-centre series serving a population of 1.5 million. METHODS: Data on clinical (n = 27) and pathological (n = 23) variables for 166 women with a diagnosis of AC treated between 2000 and 2013 were extracted from their charts and pathology reports. Overall survival (OS) was calculated, and significant determinants were identified using Kaplan-Meier analyses and log-rank tests, respectively (Canadian Task Force Classification II-2). RESULTS: This was a heterogeneous group of women with all stages of disease treated with conization, surgery, radiation, and systemic chemotherapy, alone or in combination. Mean age at diagnosis was 43; 86.7% had stage I disease, 9.6% had stage II, and only 3.6% had stage III and IV disease. Mean follow-up was 108 months. Many histotypes were diagnosed and grouped as mucinous (n = 103), endometrioid (n = 15), rare (n = 9), and adenosquamous (n = 39) types. Twenty-eight women had recurrent cancer and died of the disease; OS at 5 years was 85%. Five-year OS for women with stage I was 92%, compared with 40% for stage II or higher. Univariate analysis revealed that premenopausal status, tumour size, first-line treatment with chemotherapy, lymphovascular invasion, rare histological subtypes, stage, and receipt of second-line treatment were all significantly associated with a lower OS. Using multivariate analysis, only stage remained an independent factor. CONCLUSION: This is the largest single-centre Canadian series of invasive AC. Stage is the strongest prognostic factor in multivariate analysis; in contrast to other studies, lymph node status was not a significant determinant.

Cervical Adenocarcinoma: A Comparison of the Reproducibility of the World Health Organization 2003 and 2014 Classifications.

OBJECTIVE: The aim of the study was to compare the reproducibility of malignant glandular tumors of the uterine cervix classified per World Health Organization (WHO) 2003 and 2014. MATERIALS AND METHODS: Two pathologists reviewed 228 cases composed of adenocarcinoma in situ and 22 adenocarcinoma histotypes and selected 405 representative hematoxylin and eosin slides, which were digitally scanned. Six other pathologists (3 gynecological and 3 anatomical) independently reviewed and classified the images per both WHO classifications. One year later, they classified a random sample of 25 cases. Inter- (inter-OR) and intra-observer (intra-OR) reproducibility of the 6 pathologists and separately for gynecological compared with anatomical pathologists was tested using κ statistics. RESULTS: Both classifications were collapsed into 6 categories as benign, adenocarcinoma in situ, and mucinous, endometrioid, rare, and adenosquamous-miscellaneous carcinomas. WHO 2014 had an additional category: endocervical adenocarcinoma, usual type. Inter-observer κ values were more reliable than the intra-OR results based on 95% CIs. The average inter-OR κ values with both classifications were moderate between the 6 pathologists and between the 3 anatomical pathologists. In contrast, they were substantial between the 3 gynecological pathologists. With both classifications, the average intra-OR κ values of the 6 pathologists and both pathologist groups trended toward substantial. CONCLUSIONS: Reproducibility among 6 pathologists is unaffected by changes in the WHO 2014 classification and averages moderate between different and trends toward substantial between the same pathologist. Reproducibility between different pathologists can improve to substantial when they have expertise in gynecological pathology.

The Role of SATB2 as a Diagnostic Marker of Sinonasal Intestinal-type Adenocarcinoma.

BACKGROUND: Intestinal-type adenocarcinoma (ITAC) of the nasal cavity and paranasal sinuses is an uncommon tumor associated with exposure to wood and leather dust, nickel, and possibly smoking. ITAC shares phenotypical features with colorectal carcinoma. In contrast to most non-intestinal-type sinonasal adenocarcinomas, ITAC is an aggressive adenocarcinoma with poor clinical outcome; therefore, its reliable separation from non-ITAC is very important. AIM: The use of a combination of immunohistochemical markers of intestinal differentiation was tested in a cohort of sinonasal carcinomas of different types. The aim of this study was to explore a new intestinal marker, SATB2, in conjunction with CDX2 and CK20 in differential diagnosis of sinonasal adenocarcinomas. MATERIALS AND METHODS: Seven ITACs, 66 non-ITACs, and 1 case of extensive intestinal metaplasia (IM) of the nasal mucosa were included in the study and stained with SATB2, CK20, CDX2, and CK7 antibodies. Detection of mismatch repair proteins was performed in all cases of ITAC. All 7 sinonasal ITACs have been tested for KRAS, NRAS, and BRAF gene mutations. RESULTS: All ITACs showed positive expression for SATB2, whereas all non-ITAC cases were negative. The only 1 case of IM was found to be positive for SATB2, whereas the same case showed negative expression of CK20 and only focal immunostaining for CDX2. The genetic analysis showed that only 1 sinonasal ITAC (1/7) showed KRAS c.35G>C, p.(Gly12Ala) mutation, whereas BRAF and NRAS genes were wild type. Four ITACs revealed wild-type KRAS, NRAS, and BRAF, and 2 remaining cases were not analyzable. All ITACs showed preserved nuclear expression of mismatch repair proteins. CONCLUSIONS: SATB2 in combination with CDX2 and CK20 differentiates sinonasal ITAC from non-ITAC with increased diagnostic sensitivity and specificity and detects IM in the sinonasal tract more easily.

Interobserver agreement for Polyomavirus nephropathy grading in renal allografts using the working proposal from the 10th Banff Conference on Allograft Pathology.

A classification schema for grading Polyomavirus nephropathy was proposed at the 2009 Banff allograft meeting. The schema included 3 stages of Polyomavirus nephropathy: early (stage A), florid (stage B), and late sclerosing (stage C). Grading categories for histologic viral load levels were also proposed. To examine the applicability and the interobserver agreement of the proposed Polyomavirus nephropathy grading schema, we evaluated 24 renal allograft biopsies with confirmed Polyomavirus nephropathy by histology and SV40. Four renal pathologists independently scored the Polyomavirus nephropathy stage (A, B, or C), without knowledge of the clinical history. Viral load was scored as a percent of tubules exhibiting viral replication, using either a 3-tier viral load score (1: ≤1%; 2: >1%-10%; 3: >10%) or a 4-tier score (1: ≤1%; 2: >1%-≤5%; 3: >5%-15%; 4: >15%). The κ score for the Polyomavirus nephropathy stage was 0.47 (95% confidence interval, 0.35-0.60; P < .001). There was a substantial agreement using both the 3-tier and the 4-tier scoring for the viral load (Kendall concordance coefficients, 0.72 and 0.76, respectively; P < .001 for both). A better complete agreement was found using the 3-tier viral load score. In this first attempt to evaluate the interobserver reproducibility of the proposed Polyomavirus nephropathy classifying schema, we demonstrated moderate κ agreement in assessing the Polyomavirus nephropathy stage and a substantial agreement in scoring the viral load level. The proposed grading schema can be applied in routine allograft biopsy practice for grading the Polyomavirus nephropathy stage and the viral load level.

Immunohistochemical and morphologic findings in columnar cell lesions of the breast.

BACKGROUND: Columnar cell lesions (CCLs) with or without atypia frequently coexist with invasive or in situ breast carcinomas. In this study, 39 mastectomy specimens containing CCLs coexisting with invasive carcinomas were retrospectively analyzed for cellular characteristics and structural pattern of CCL neighboring the tumor. MATERIALS AND METHODS: The expression of estrogen receptor (ER), progesterone receptor (PR), and p53 antibodies in CCL and coexisting invasive tumors, type of invasive tumor, histopathologic grade, and presence of atypia in CCL have been studied. RESULTS: Sixteen (41%) of all CCLs were with atypia, whereas 23 (59%) of them were without atypia. No correlations were found between the presence of CCLs with atypia and either the morphologic type of carcinoma or histopathologic grade of the tumors. Presence of atypia in the CCL was not correlated with the expression of p53 in the invasive tumors. CCLs without atypia dominated in Grade III tumors. The percentages of CCLs without atypia were also higher in both ER (-) and PR (-) tumors. CONCLUSIONS: CCL with atypia is generally considered to be a precursor of invasive carcinoma; however, in our study, CCLs without atypia more frequently coexisted with breast carcinoma.

Graft inflammation and histologic indicators of kidney chronic allograft failure: low-expressing interleukin-10 genotypes cannot be ignored.

BACKGROUND: Infiltration of inflammatory cells into the renal allograft interstitium is the biologic hallmark of alloimmune responses that leads to tubulointerstitial injury and subsequent interstitial fibrosis and chronic allograft failure. The proliferation, stimulation, and infiltration of these inflammatory cells are governed by various proinflammatory and regulatory cytokines. We assessed whether the differences in the genes encoding cytokines (producing low, moderate, or high expression profiles) may affect the infiltration of inflammatory cells into the renal allograft and the histologic changes characteristics of chronic allograft failure. METHODS: A total of 218 kidney transplant recipients were genotyped for 15 single-nucleotide polymorphisms located in the gene promoter or exonic regions of 10 different cytokines or their receptors. Six- to 12-month posttransplant surveillance biopsies were scored using 11 individual histologic parameters and the combined grade of interstitial fibrosis and tubular atrophy (IF/TA). B-cell, T-cell, and macrophage infiltrates were quantified by immunostaining. RESULTS: The low-expressing interleukin (IL)-10 gene promoter genotypes were found significantly associated with high IF/TA grade (IL-10 -819 TT; P=0.035; odds ratio=3.27; 95% confidence interval 1.1-9.8). At individual histologic indices, recipients carrying low-expressing IL-10 genotypes showed 2.5-fold higher scores for interstitial fibrosis, inflammation, and tubular atrophy. High infiltration of T cells and macrophages but not B cells into the renal allograft interstitium was found strongly associated with the carriage of low-expressing IL-10 genotypes. CONCLUSIONS: The results suggest that renal transplant recipients genetically predisposed to low expression of the regulatory cytokine IL-10 are more susceptible to high grades of IF/TA scores, graft inflammation, and high influx of inflammatory cells into the graft interstitium.

Histopathologic features aid in predicting risk for progression of IgA nephropathy.

BACKGROUND AND OBJECTIVES: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide. Accurately identifying patients who are at risk for progressive disease is challenging. The extent to which histopathologic features improves prognostication is uncertain. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a retrospective cohort with biopsy-proven IgAN in Calgary, Canada. Renal biopsies were reviewed by a nephropathologist with histopathologic data abstracted using a standardized form. The primary outcome was the composite of doubling of serum creatinine, ESRD, or death. Spline models defined significant levels of interstitial fibrosis, glomerulosclerosis, hypertension, proteinuria, and creatinine. The prognostic significances of clinical and histopathologic parameters were determined using Cox proportional hazards models. RESULTS: Data from 146 cases were available for analysis with a median follow-up of 5.8 years. Greater than 25% interstitial fibrosis, >40% glomerular sclerosis, and a systolic BP >150 mmHg were risk thresholds. In univariable analyses, baseline creatinine, proteinuria, systolic BP, glomerular sclerosis, interstitial fibrosis, and crescentic disease were predictors of the primary outcome. In multivariable models adjusted for clinical characteristics, interstitial fibrosis (hazard ratio [HR]2.7; 95% confidence interval [CI] 1.2 to 6.0), glomerular sclerosis (HR 2.6; 95% CI 1.2 to 4.5), and crescents (HR 2.4; 95% CI 1.2 to 5.1) remained independent predictors of the primary outcome and significantly improved model fit compared with clinical characteristics alone. CONCLUSIONS: Baseline histopathologic parameters are independent predictors of adverse outcomes in IgAN even after taking into consideration clinical characteristics. Relatively small degrees of interstitial fibrosis confer an increased risk for progressive IgAN.

Identification and characterization of demethylase JMJD1A as a gene upregulated in the human cellular response to hypoxia.

Hypoxia is commonly found in human solid cancers and serves as a selective environment for the survival of aggressive cancer cells and as protection from anti-cancer therapies. In addition to a shift to anaerobic metabolism, the cellular response to hypoxia includes cessation of cell division and/or cell death. These mechanisms have still not been defined. Identification of the members of hypoxia-induced growth arrest pathways remain incomplete. We have undertaken an expression microarray analysis of the cellular response to hypoxia in diverse cell lines. An identified cohort of genes is reliably upregulated in various cells in response to hypoxia, as validated by reverse-transcriptase polymerase chain reaction (RT-PCR). One of the upregulated targets corresponds to an expressed sequence tag encoded by JMJD1A (a gene also known as JHDM2A), which has been identified as a histone demethylase that regulates the transcription of androgen receptor targets. We confirm, by RT-PCR, the upregulation of JMJD1A after hypoxia and desferroxamine treatment in multiple cell lines. We also show that JMJD1A is predominantly, but not exclusively, a nuclear protein. Immunofluorescent staining of HeLa cells shows a shift of cytoplasmic JMJD1A into the nucleus on hypoxia treatment. Immunohistochemical staining has revealed that JMJD1A is widely expressed in tissues, even in cells that are not known to express the androgen receptor, and is significantly increased in smooth muscle cells upon hypoxia treatment.

Mutation or polymorphism of the CD20 gene is not associated with the response to R-CHOP in diffuse large B cell lymphoma patients.

BACKGROUND: Rituximab, a chimeric antibody targeted to the human CD20 molecule, is a major component of the R-CHOP protocol used to treat patients with diffuse large B cell lymphoma (DLBCL). It is also a very expensive drug. Though the response rate of R-CHOP is higher than that of CHOP alone, patients may still experience a poor response. One possible mechanism that may mediate the poor response to R-CHOP is poor binding of the drug to the CD20 molecule, perhaps due to mutations or polymorphisms of the CD20 gene that affect its structure. To test this hypothesis and perhaps define a new predictor of R-CHOP response, our pilot study evaluated the CD20 gene sequence from patients exhibiting a poor outcome to R-CHOP. METHODS: Eleven patients with DLBCL who exhibited a recurrence of their disease and/or died within 24 months of R-CHOP treatment were categorized as showing poor progression-free survival (poor outcomes). Paraffin-embedded tissue specimens from the original tumors were evaluated for mutations or polymorphisms of the CD20 gene. Furthermore, sections from these patients and as well as from matched control patients who were categorized as good outcome patients (no progression of their disease within 36 months) were stained with anti-CD20 antibody and compared for CD20 protein expression. RESULTS: DNA sequence analyses revealed that no mutations were observed in DNA from the coding region of the CD20 gene in any of the initial tumors from 11 patients who showed poor outcomes with R-CHOP therapy. One case showed a synonymous single nucleotide polymorphism in exon 2 (C216T; rs2070770; Ile>>Ile). No significant differences in CD20 expression was observed between good and poor outcome patients with R-CHOP. CONCLUSIONS: Our results do not support association of CD20 mutations in specimens of the initial tumor or structural polymorphisms of the CD20 gene with patients who exhibited poor outcomes to R-CHOP.

Pathogenesis and management of chronic allograft nephropathy.

Chronic allograft nephropathy (CAN) is a common cause of late kidney transplant failure, characterized by progressive histological damage in the allograft. Although functional biomarkers such as creatinine are typically used to predict CAN, recent evidence suggests that composite, quantitative histological indices may be better predictors of long-term graft outcomes. Calcineurin inhibitors (CNIs) have been associated with major improvements in early rejection outcomes, but appear to cause both acute and chronic nephrotoxicity. The acute phase is associated with functional nephrotoxicity and is reversible with a reduction in CNI dosage, whereas the chronic phase is characterized by persistent histological lesions that are typically irreversible. Results from recent clinical trials suggest that converting from a CNI to sirolimus, withdrawing a CNI from a sirolimus-based regimen or using a CNI-free strategy may improve long-term outcomes by reducing CNI-related nephrotoxicity. However, in the de novo transplant setting, triple therapy with sirolimus, mycophenolate mofetil and corticosteroids is not recommended in combination with basiliximab induction. A treatment algorithm, based on the patient's histological score obtained on an allograft biopsy taken at approximately 6-12 months post-transplant, has been developed by our group and is described here.

Evaluating the accuracy of functional biomarkers for detecting histological changes in chronic allograft nephropathy.

The most common cause of late kidney transplant failure is chronic allograft nephropathy (CAN). Much research has focused on identifying biomarkers (or correlates) that would predict subsequent CAN and allow timely intervention. Functional biomarkers such as serum creatinine and estimated glomerular filtration rate (eGFR) have been widely adopted, even though they have not been rigorously evaluated as surrogate markers. This study evaluated serum creatinine and eGFR for predicting the early histopathological changes seen in transplant protocol biopsies (TPB). We prospectively followed 289 kidney transplant patients in the Southern Alberta Transplant Program who had TPB at 6-12 months post-transplant. Tissue samples (n = 280) were independently examined by renal pathologists. The ability of serum creatinine or eGFR to predict the threshold level for abnormal histopathology was evaluated by calculating the area under the receiver operator characteristic curve. Serum creatinine and eGFR had poor predictive value (most confidence intervals included 0.5, indicating no predictive ability) for ten individual histological measurements (Banff 97 scores), and the Chronic Allograft Damage Index. We conclude that serum creatinine and eGFR have a limited clinical role in predicting the early histopathological changes that precede CAN and should not be used for this purpose.

Malignancy risk of small polyps and related factors.

The aim of this study was to determine the risk of polyps <6 and between 6 and 10 mm in terms of progression to malignancy and to evaluate the influence of age, gender, and colonic localization on malignancy development. Thirteen hundred sixty-nine polyps <10 mm identified in 680 patients were retrospectively evaluated. Sixty-seven and two-tenths percent of polyps <10 mm were of a neoplastic nature. The incidence of neoplasia was higher in left-sided and small polyps than diminutive polyps. In patients older than 60 years, small polyps showed a higher rate of high-risk histology than diminutive polyps,while the same relationship did not exist in other age groups. In male patients over 60 years of age, the rate of high-risk histology was higher in small polyps than in diminutive polyps.

The importance of glomerular deposits of von Willebrand factor in human renal allografts.

OBJECTIVE: The aim of this study was to evaluate the importance of glomerular expression of von Willebrand factor (vWF) in human renal allografts. METHODS: We investigated graft biopsies from 72 renal transplant recipients, 40 with acute rejection (AR) and 32 with chronic allograft nephropathy (CAN). All biopsy specimens were immunostained with vWF and CD68 and graded using 3-tiered scales. The follow-up biopsies of patients with AR were reevaluated for development of glomerular sclerosis. RESULTS: A significant difference was found between type 1 and type 2 AR with regard to glomerular vWF expression (P < 0.01). None of the patients with type 1 AR showed mesangial vWF expression, but 36.4% of patients with type 2 AR showed segmental mesangial vWF expression. In follow-up biopsies, 18 of 40 patients developed significant glomerular sclerosis, and patients with mesangial vWF expression (grade 3 GvWF) showed glomerular sclerosis earlier than did others (P < 0.01). In addition, the outcome for grafts that showed grade 3 glomerular vWF was significantly worse than was the outcome noted for grafts that showed grade 1 or grade 2 glomerular vWF (P < 0.001). Half of the biopsy specimens in the CAN group showed global mesangial vWF expression. Glomerular macrophage infiltration was correlated with degree of glomerular vWF expression both in the AR and in the CAN groups (P < 0.05, P= 0.001, respectively). CONCLUSION: We hypothesized that the increasing amount of glomerular vWF may be used as a marker of acute vascular rejection and may help for the evaluation of renal allograft biopsies without sufficient arteries. In addition, it can also be a marker for development of early glomerular sclerosis and may help us determine which patients are in need of further treatment.

Chordoid meningioma: rare variant of meningioma.

Chordoid meningioma is a rare variant of meningioma that bears a striking histological resemblance to chordoma and has greater likelihood of recurrence. Although most meningiomas occur in the intracranial, orbital and intravertebral cavities, rare meningiomas have been reported in extracranial organs; thus, it is important to be able to distinguish them from other neoplasms that have similar histology but different biological behavior and therapies. A case of chordoid meningioma in a 48-year-old woman who did not have Castleman's syndrome is described in the present report. The patient presented with a mass in her left frontoparietal region, and had been suffering from headaches for many years. Magnetic resonance imaging of the brain demonstrated an expansive lytic lesion in the squamous portion of the left temporal bone. The lesion extended in both directions. Histological examination of the surgical specimen revealed a tumor composed of cords and nests of eosinophilic vacuolated cells embedded in a myxoid matrix. A typical meningiomatous pattern was observed focally, and positive staining of the tumor cells for vimentin and epithelial membrane antigen confirmed the diagnosis of chordoid meningioma.

Cystic lymphangioma confined to mediastinum in an adult.

Mediastinal lymphangiomas are very rare tumors among the slow-growing mediastinal masses in the literature. We present the successful resection of a 52-year-old woman who was referred to our hospital. Past medical history consisted of surgical treatment for cervical mass and pathological diagnosis of lymphoma nine years earlier. She underwent postoperative radiotherapy. Preoperative chest roentgenogram and computed tomogram of the chest showed a cystic mass in the anterior mediastinum. The tumor was completely resected. The preoperative diagnosis was never questioned until the histopathological examination confirmed that the lesion was a cystic lymphangioma. Cystic lymphangiomas are benign tumors with the evidence of progression in tumor size and invasion into the vital structures. As our case shows, the tumor involvement with the vital structures causes difficulty in removal.