Kaposi’s sarcoma (KS) is a rare endothelial neoplasm mainly involving the skin, but it is often associated with AIDS. Diagnosis of gastrointestinal (GI) tract KS, a common site of visceral involvement in AIDS, is important, but endoscopic biopsy carries a risk of false-negative results (FNRs) due to its submucosal appearance. This study sought to determine the rate and causes of FNR for endoscopic biopsy of GI-KS lesions. Endoscopic biopsy samples of 116 GI-KS lesions were reviewed retrospectively. All GI-KS lesions were confirmed to be resolved following KS therapy. FNRs were yielded for 41 of the lesions (35.3%). Among upper and lower GI sites, the esophagus was the only site significantly associated with FNRs (
Kaposi’s sarcoma (KS) is a cancer of the lymphatic and blood vessels that mainly involves the skin [
KS can also involve the oral cavity, lymph nodes, and viscera [
The purpose of this study was to determine the rate and causes of FNR from endoscopic biopsies of GI-KS lesions.
Histopathology slides of endoscopic biopsy samples of 116 consecutive, GI-KS lesions from 24 HIV-infected patients who had not received anti-KS therapy were retrospectively reviewed. All biopsies were performed between 2002 and 2006 at the National Center for Global Health and Medicine (NCGM), a 900-bed hospital located in the Tokyo metropolitan area with the largest referral center for HIV/AIDS in Japan.
The institutional review board at NCGM approved this study. All patients from whom clinical samples were obtained during endoscopic biopsy provided written informed consent prior to the procedure. Data obtained from the patient medical records was anonymized before analysis.
HIV infection route was determined by the medical staff who interviewed each patient on the first visit to our hospital. Routes of HIV infection were determined by medical staff who questioned each patient face to face on the first visit to our hospital. Routes were classified into six categories: homosexual, bisexual, heterosexual, drug user, untreated blood products, and unknown. Patients who were homosexual or bisexual were regarded as men who have sex with men (MSM).
CD4+ cell counts were checked within 1 week of endoscopy. HIV-RNA viral loads (VLs) determined by real-time quantitative polymerase chain reaction (PCR) were reviewed within 1 month of endoscopy. The minimum detection level was 40 copies/mL of plasma. A positive result for real-time HIV-RNA was defined as ≥40 copies/mL.
Biopsy was performed using biopsy forceps (FB-240U, FB230-K; Olympus Co., Tokyo, Japan). All biopsies were performed by well-trained endoscopists (experience of >1.000 colonoscopies).
A definitive diagnosis of GI-KS was defined as follows. Negative results confirmed from biopsy samples for other GI diseases such as infection, inflammatory bowel disease, hyperplastic polyp, fundic gland polyp, inflammatory polyp, adenomatous polyp, angioectasia, GI lymphoma, premalignant lesion, esophageal cancer, gastric cancer, and colorectal cancer. Presence of proliferating spindle cells (Figure Positive response to KS therapy (HAART or systemic therapy of liposomal anthracycline); in particular, for visible GI-KS lesions without typical pathological findings from biopsy specimens, partial or complete resolution confirmed on follow-up endoscopy following KS therapy.
Pathological features of GI-KS on HE staining. (a) Low-power view showing a distinct proliferative lesion within the submucosa of the small bowel intestine. (b) High-power view showing spindle cell proliferation with vascular channel formations filled with blood cells.
GI-KS was evaluated in terms of site, size (≤10 mm or >10 mm), and macroscopic findings on endoscopy. Site of GI involvement was classified into 7 regions: esophagus, stomach, duodenum, ileum, right-side colon (cecum, ascending colon, and transverse colon), left-side colon (descending colon and sigmoid colon), and rectum. Macroscopic findings were evaluated in the presence of reddish mucosa with patches (Figure
Gastrointestinal Kaposi’s sarcoma on endoscopy. (a) Dark reddish patch lesion (arrow) in the esophagus. (b) Small (≤10 mm) and polypoid lesion in the duodenum. (c) Submucosal tumor-like lesion with ulceration in the stomach. (d) Bulky tumor mass surrounding the anorectal area causing anorectal stenosis.
The descriptive patient characteristics were summarized, and the absence rate of spindle cells or vascular formations on pathology for the 116 samples was then analyzed to elucidate the FNR rate of endoscopic biopsy. To determine the cause of FNRs, the relationships between FNR and endoscopic findings (size, site, macroscopic appearance) were evaluated using the
Values of
Characteristics of the 24 patients are shown in Table
Baseline characteristics of GI-KS patients (
Age, years (IQR) | 39 (34.5–49.5) |
Sex, male (%) | 24 (100) |
MSM | 24 (100) |
CD4 cell counts, cells/mL (IQR) | 71 (15.5, 177.5) |
HIV viral load, copies/mL (IQR) | 115,000 (2,900, 145,000) |
GI symptoms (%) | 8 (33.3%) |
IQR: interquartile range; GI: gastrointestinal; MSM: men who have sex with men.
A total of 113 GI-KS lesions were from 24 HIV-infected patients (Table
Macroscopic appearances of GI-KS on endoscopy according to the GI site (
|
Patches ( |
Polypoid ( |
SMT ( |
SMT with ulcer ( |
Bulky tumor ( |
---|---|---|---|---|---|
Upper GI | 15 (37.5%) | 0 | 33 (71.7%) | 19 (73.1%) | 0 |
Esophagus | 3 (7.5%) | 0 | 1 (2.2%) | 0 | 0 |
Stomach | 4 (10.0%) | 0 | 18 (39.1%) | 10 (38.5%) | 0 |
Duodenum | 8 (20.0%) | 0 | 14 (30.4%) | 9 (34.6%) | 0 |
Lower GI | 25 (62.5%) | 1 (100%) | 13 (28.3%) | 7 (26.9%) | 3 (100%) |
Ileum | 5 (12.5%) | 1 (100%) | 0 | 0 | 0 |
Right-side colon | 9 (22.5%) | 0 | 6 (13.0%) | 5 (19.2%) | 0 |
Left-side colon | 5 (12.5%) | 0 | 6 (13.0%) | 1 (3.9%) | 0 |
Rectum | 6 (15.0%) | 0 | 1 (2.2%) | 1 (3.9%) | 3 (100%) |
GI: gastrointestinal; SMT: submucosal tumor.
No clinical complications of GI-KS lesions were seen. There were no significant gastrointestinal bleeds or perforations, either spontaneous or after endoscopic biopsy. Diagnostic yield of GI-KS is shown in Table
Rate and causes of false-negative endoscopic biopsy results for GI-KS lesions on univariate analysis.
|
GI-KS lesions | Lesions with true-positive results | Lesions with false-negative results |
|
---|---|---|---|---|
( |
( |
( |
||
Site |
|
|
|
|
Upper GI tract | 67 (57.8%) | 39 (68.3%) | 28 (52.0%) | 0.09 |
Esophagus | 4 (3.45%) | 0 | 4 (9.76%) |
|
Stomach | 32 (27.6%) | 19 (25.3%) | 13 (31.7%) | 0.46 |
Duodenum | 31 (26.7%) | 20 (26.7%) | 11 (26.8%) | 0.99 |
Ileum | 6 (5.17%) | 5 (6.67%) | 1 (2.44%) | 0.33 |
Lower GI tract | 49 (42.2%) | 36 (48.0%) | 13 (31.7%) | 0.09 |
Right-side colon | 20 (17.2%) | 15 (20.0%) | 5 (12.2%) | 0.29 |
Left-side colon | 12 (10.3%) | 8 (10.7%) | 4 (7.32%) | 0.88 |
Rectum | 11 (9.48%) | 8 (10.7%) | 3 (7.32%) | 0.56 |
Size <10 mm | 23 (19.8%) | 10 (13.3%) | 13 (31.7%) |
|
Macroscopic appearance |
|
|
|
|
Patches | 40 (34.5%) | 18 (24.0%) | 22 (53.7%) |
|
Polypoid lesion | 1 (0.86%) | 1 (1.33%) | 0 | 0.46 |
SMT | 46 (39.7%) | 31 (41.3%) | 15 (36.6%) | 0.62 |
SMT with ulcer | 26 (22.4%) | 22 (29.3%) | 4 (9.76%) |
|
Bulky mass | 3 (2.59%) | 3 (4.00%) | 0 | 0.19 |
GI: gastrointestinal; SMT: submucosal tumor.
Among the GI locations, the esophagus was significantly (
On multivariate analysis, the esophageal site and a patch pattern on endoscopy were independently associated with FNR (Table
Factors associated with false-negative endoscopic biopsy results in GI-KS lesions on multivariate analysis (
Odds ratio | 95% CI |
| |
---|---|---|---|
Esophageal site | 7.26 | 0.82–∞ | 0.08 |
Patches on endoscopy | 3.30 | 1.33–8.36 | <0.01 |
GI: gastrointestinal; CI: confidential interval.
Endoscopy is clearly a valuable diagnostic method for identifying GI-KS, but it may produce FNR. Firstly, we found that FNR were yielded in 41 of the 116 lesions (35.3%) in this study. Previous studies on GI-KS patients have also reported a relatively low diagnostic yield for endoscopic biopsy [
Various clinical factors can contribute to FNR on biopsy. Submucosal location or tumor growth is considered to account for the poor diagnostic yield of standard forceps biopsies [
Secondly, with regard to the GI site, we found the esophagus to be the only site associated with FNR on both univariate and multivariate analyses. In this study, we assessed the site by dividing the GI into 7 parts. Because it is difficult to differentiate the ascending colon from the cecum and the descending colon from the sigmoid colon on endoscopy, we divided the colon into the right-side and left-side colon. No other study has divided the GI tract into small segments and investigated the diagnostic yield in such detail as in the present study. The yield of endoscopic biopsy in the upper GI tract has been estimated as 13%, which is low compared with 36% on sigmoidoscopy [
Thirdly, in terms of the endoscopic appearance of GI-KS, small lesions (<10 mm) and patches were found to be significantly associated with FNR on univariate analysis. Because such characteristics could be confounding factors, we performed multivariate analysis and found that patches were correlated with FNR as an independent factor. We suggested that these lesions contain only a small amount of tumor tissue, which made such biopsy specimens too small to be diagnostically useful. On the other hand, the finding of “SMT with ulceration” was significantly associated with true-positive results, and these lesions were easily diagnosed by biopsy. This result may be attributable to the ulcerous appearance of the tumor, which makes it easy to obtain samples from the submucosal layer [
Fourth, we found that endoscopic biopsy is a safe diagnostic method for GI-KS even in the presence of an ulcerative or bulky tumor. A previous report [
Endoscopists and clinicians should become familiar with characteristic endoscopic images of GI-KS and recognize that the diagnostic yield of GI-KS varies depending on the morphological features. In addition, pathologists should carefully evaluate lesions associated with FNR. Because KS-related GI lesions indicate visceral involvement, the indications for and selection of HAART and systemic chemotherapy need to be considered [
Endoscopic biopsy is essential for diagnosing GI-KS and it is a safe method. While FNR were found in 35.3% of lesions, FNRs differed according to a lesion site, size, and macroscopic appearance. On endoscopic biopsy, FNR was related with early-stage KS (small size or patches appearance) and site of esophagus, whereas SMT with ulceration is relatively easy to diagnose. Caution should be exercised when performing endoscopic biopsy of these lesions in AIDS patients and evaluating the histological features.
The authors declare that they have no conflict of interests.
This work was supported by a Grant from the National Center for Global Health and Medicine (21-101).
The authors wish to thank Hisae Kawashiro, Clinical Research Coordinator, for assistance with data collection.