Immediate histopathologic correlation in Turkish population with negative cytology and high-risk human papillomavirus positivity: A retrospective analysis of high-risk human papillomavirus genotype and stratified by age.

INTRODUCTION: According to the American Society of Colposcopy and Cervical Pathology (ASCCP) recommendations, regardless of age, women with high-risk infections other than human papillomavirus 16/18 positivity (other hrHPV) and negative cytology should not be referred directly to colposcopy. Several studies compared detection rates of ≥high-grade squamous intraepithelial lesion (HSIL) between HPV 16/18 ± 45, and other hrHPV types on colposcopic biopsy. METHODS: We designed a retrospective study to determine the presence of ≥HSIL in colposcopic biopsy in women with negative cytology and hrHPV positivity during the years 2016-2022. RESULTS: HPV 16/18/45 had a PPV of 43.8%, while other hrHPV types had a PPV of 29.1% for a tissue diagnosis of ≥HSIL. For a tissue diagnosis of ≥HSIL detection, there was no statistically significant difference between the PPV of other hrHPV and HPV 16/18/45 in patients ≥30. There were only two cases with a tissue diagnosis of ≥HSIL in the other hrHPV group of women under 30 years of age. CONCLUSION: We suggested that the follow-up recommendations of ASCCP for patients above the age of 30 with negative cytology and other hrHPV positivity may not be fully applicable to countries like Turkey with a different healthcare environment. Referring to patients ≥30 who had other hrHPV positivity and negative cytology to direct colposcopy may be clinically beneficial, particularly in populations where a colposcopic examination is easy and inexpensive.

Comparison of the Clinical Performance of Aptima HPV Assay and the Cobas 4800 Platform in Women with Normal Cytology and Positive High-Risk HPV.

INTRODUCTION: According to the current American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines, patients with normal cytology results may be referred for colposcopy according to their high-risk human papillomavirus (hrHPV) test results. A higher positive predictive value (PPV) of hrHPV has significance for preventing unnecessary colposcopic examinations. Several studies have compared the performance of the Aptima assay and the Cobas 4800 platform among patients who had minor cytologic abnormalities. However, in our English literature search, we found no other study that had been conducted to compare these two methods in patients with normal cytology. We thus aimed to compare the PPV of the Aptima assay and the Cobas 4800 platform among women with normal cytology. METHODS: Between September 2017 and October 2022, we retrospectively identified 2,919 patients who had normal cytology and hrHPV positivity and had been referred for a colposcopy. Among them, 882 agreed to undergo a colposcopy; on examination, 134 had target lesions revealed and underwent a colposcopic punch biopsy. RESULTS: Among the patients who underwent a colposcopic punch biopsy, 49 (38.9%) were tested with Aptima, and 77 (61.1%) were tested with Cobas. In the Aptima group, 29 (59.2%) patients showed benign histology, 2 (4.1%) patients had low-grade squamous intraepithelial lesions (LSILs), and 18 (36.7%) patients had ≥high-grade squamous intraepithelial lesions (HSILs) biopsy results. The false-positivity rate and PPV of Aptima were 63.3% (31/49) and 36.7% (95% confidence interval [CI]: 0.232-0.502), respectively, for a histopathologic diagnosis of ≥HSIL. In the Cobas group, 48 (62.3%) biopsies were benign, 11 (14.3%) reported an LSIL, and 18 (23.4%) biopsies were ≥HSIL. The false-positivity rate and PPV of Cobas were 76.6% (59/77) and 23.4% (95% CI: 0.139-0.328), respectively, concerning a ≥HSIL tissue diagnosis. The false-positivity rate of Aptima HPV 16 positivity was 40% (4/10). The false-positivity rate of Cobas HPV 16 positivity was 61.1% (11/18). The PPVs of HPV 16 positivity for Aptima and Cobas were 60% (95% CI: 0.296-0.903) and 38.9% (95% CI: 0.163-0.614), respectively, concerning ≥HSIL tissue diagnosis. CONCLUSION: We recommend analyzing the performances of hrHPV platforms in future, larger studies in patients with normal cytology rather than only in cases with abnormal cytology.

Prognostic value of the lymph node ratio in surgically treated stage III colorectal cancer patients with high numbers of harvested lymph nodes.

BACKGROUND: The lymph node ratio (LNR), defined as the number of positive lymph nodes (LN) divided by the total number of harvested LN, has been demonstrated to be an independent factor in the prognosis of surgically treated colorectal cancer (CRC) patients. This study aims to establish the prognostic value of LNR in stage III CRC patients with high numbers of LN removed. METHODS: Stage III CRC patients who underwent curative resections over an 8-year period were included to the study. Demographics, clinicopathological features, surgical as well as recurrence and survival outcomes were recorded and statistically analyzed. Calculations for LNR were carried out as a function of percentage rates and Cox proportional hazards regression analyses were performed to determine its effect on disease-free and overall survival. RESULTS: Among a total of 493 surgically treated CRC cases, 104 patients were included to the study consisting of 68 (65.4%) men and 36 (34.6%) women with a median age of 64 (inter-quartile range: 55-74) years. The mean number of harvested LN was 31.6 ± 21.0 (range: 12-103). Multivariate Cox regression analyses proved LNR to be a significant factor in both disease-free and overall survival (p = 0.007 and p = 0.003, respectively). Forward elimination analyses showed that a 1% increase in LNR resulted with a 2% increase in both the risks of recurrence and mortality. CONCLUSIONS: The LNR may be assessed as an adjunct to the current staging systems for the prediction of oncological outcomes and survival of surgically treated stage III CRC patients.

Bilateral Native Kidney Papillary Renal Cell Carcinomas in a 11-Year-Old Renal Transplant Patient.

Renal cell carcinomas (RCCs) are the most common renal tumors in adults and are usually sporadic and unilateral. Renal transplant recipients have an increased risk of developing RCC. RCC development after kidney transplantation is very rarely reported in children. We present a 11-year-old boy who had cadaveric kidney transplantation for kidney failure 2 years ago. He was under immunosuppressive therapy and presented with microscopic hematuria. An ultrasound (US) revealed bilateral solid renal masses. Further cross-sectional imaging showed a 60 × 70 × 60-mm right renal mass with claw sign and a 5 × 6 × 6-mm mass in the left renal lower pole. A bilateral radical nephroureterectomy of native kidneys was performed. The pathology revealed bilateral papillary RCC without TFE3 upregulation. The patient was kept on low-dose immunosuppressive therapy in the perioperative period. He received no chemotherapy but a close radiological surveillance was undertaken. He is tumor-free 2 years after the operation. RCC is a rare tumor for children and bilateralism is even rarer. The child had a history of chronic kidney disease, peritoneal dialysis, and immunosuppressive therapy. As there are no standardized protocols regarding imaging in transplanted kidneys routine surveillance, US follow-up should also focus on detecting malignancy.

Comparison of the diagnostic accuracy of the updated Sydney system and single biopsy.

Background: Updated Sydney system (USS) recommends taking biopsies from certain areas of the stomach for the diagnosis of precancerous lesions associated with Helicobacter pylori. Our aim was to evaluate the contribution of each of the biopsy sites to the diagnosis. Methods: This prospective study included 97 patients aged 40 and over with dyspeptic complaints. Biopsies were taken from five regions: the lesser curvature of the antrum (LCA), the lesser curvature of the corpus (LCC), incisura angularis (IA), the greater curvature of the antrum (GCA), and the greater curvature of the corpus (GCC). Biopsy specimens were stained with hematoxylin-eosin stain, periodic acid Schiff-alcian blue, and Giemsa histochemical stain and evaluated according to the Sydney classification. Results: Thirty-seven (38%) patients were positive for H. pylori in at least one biopsy site. Atrophic gastritis without intestinal metaplasia (IM) was found in 17 (17.5%) of the patients (6.2% in IA, 5.2% in each of LCA, GCA, and LCC, and 2% in GCC). The prevalence of atrophic gastritis with IM was 42.3% (21.6% in LCA, 20.6% in GCA, 20.6% in IA, 14.4% in LCC, and 5.2% in GCC). Endoscopic follow-up was planned in 21 (22%) patients due to the presence of extensive atrophy or incomplete IM. If a single biopsy of the LCA or a biopsy of both LCA and GCA was taken, endoscopic follow-up would have been missed in 12 (57%) or 6 (29%) patients, respectively. Conclusion: Taking biopsies in accordance with the USS had higher sensitivity in detecting atrophic gastritis with or without IM compared to single biopsy. One or two biopsies is not sufficient to identify patients for whom endoscopic follow-up is recommended.

Nephroprotective Efficacy of Sugammadex in Ischemia-Reperfusion Injury: An Experimental Study in a Rat Model.

BACKGROUND: It is known that ischemia-reperfusion damage in the kidney is one of the most common causes of acute kidney failure. It is also known that reduced renal damage has a nephroprotective effect by reducing the release of inflammatory and vasoactive peptides that cause tissue damage. Therefore, we think that reperfusion caused by ischemia in kidney damage may be an important focus for clinical research. METHODS: A total of 21 healthy 230-250 g female rats were used in our experimental study. During the experiment, animals were randomly divided into three groups, each containing seven rats. Group 1: The group that underwent left nephrectomy with a sham operation. Group 2: Left renal ischemia for 60 minutes, then left nephrectomy followed by 45 minutes of reperfusion. Group 3: Left renal ischemia for 60 minutes, then reperfusion for 45 minutes, followed by left nephrectomy. In this group, sugammadex was given intravenously at a dose of 100 mg/kg at the beginning of reperfusion. In the histomorphological examination, damage findings of tubules atrophy, dilation and cast formation, tubular epithelial brush border loss and vacuolization, presence of fibrosis as interstitial structural change, capillary vasodilatation/congestion and neutrophilic cell infiltrates in interstitial spaces, and morphological changes in glomeruli were evaluated. RESULTS: When evaluated based on tubular brush border, there were no significant differences between Group 2 and Group 1 (P = 0.454), while the damage in Group 3 was less significant than Group 2 (P = 0.017). When evaluated in terms of tubular vacuolization, there was no significant difference between Group 2 and Group 1 (P = 0.902), while the damage in Group 3 was less significant than Group 2 (P = 0.017). CONCLUSION: We believe that 100 mg/kg sugammadex given at the beginning of reperfusion after one hour of ischemic condition on rats has a histochemically detectable nephroprotective effect.

Computed Tomography-based Morphological Differences between Histologic Subtypes of Periampullary Ductal Adenocarcinoma.

OBJECTIVE: To evaluate the computed tomography (CT)-based differences between pancreaticobiliary (PBST) and intestinal (IST) subtypes of periampullary pancreatic ductal adenocarcinomas (PDAC). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Faculty of Medicine, Istanbul Medeniyet University, Göztepe Training and Research Hospital, Turkey between 2015 and 2018. METHODOLOGY: Overall 24 periampullary PDAC cases, in whom histomorphologic evaluation and CDx2 expression were used to discriminate between PBST and IST, were included. The lesion morphology (infiltrative versus nodular), common bile and main pancreatic ducts' dilation, tumor grade, enhancement pattern, pancreaticoduodenal groove, pancreaticoduodenal artery and lymphatic involvement were evaluated by CT. RESULTS: Overall 24 PDAC cases [median age 67.5 (60.5-76.5) years] were enrolled. Histopathology revealed 9 (25%) IST and 18 (75%) PBST. The age [72.5 (69-81) versus 63 (57.75-75.5) years, respectively, p=0.204] and gender [3 (50%) versus 12 (66.7%) males, respectively, p=0.635] and the prevalence of all CT characteristics were similar between groups (p>0.05 for all) except for lesion morphology. Infiltrative morphology was more frequent in PBST than IST [14 (77.8%) versus 1 (16.7%), respectively, p=0.015]. Multiple variable logistic regression analysis revealed infiltrative morphology as the only independent CT predictor of PBST [OR: 14.9, 95% CI: 1.2-186), p=0.036]. The interrater reproducibility for lesion morphology was moderate (Cohen's Kappa: 0.55, p<0.007). CONCLUSION: Infiltrative appearance is associated with PBST; whereas, nodular appearance more likely predicts IST. The potential role of CT lesion morphology on guiding appropriate chemotherapy in cases with no chance for surgery or biopsy requires addressing. Key Words: Intestinal differentiation, Pancreatobiliary differentiation, Periampullary adenocarcinoma.

A Five-Year Retrospective Analysis of Basal Cell Carcinoma: A Monocentric Study.

OBJECTIVE: Our aim in this study is to define the histopathological subtypes, body site distribution, and incidence rates of single or multiple of BCCs. The study is conducted on patients from a single institution in Istanbul which has a migrant-receiving population reflecting that of the country overall. METHOD: We retrospectively analyzed data concerning 896 cases of BCC seen between 2014 and 2018. Data about patient demographics (age and sex), tumor diameter,its anatomic localization, histological type, presence of ulceration, lymphovascular/perineural invasion, and single or multiple tumor formations were retrieved from both the hospital's automated system and archived records of the pathology clinic. RESULTS: Our univariate analysis showed that the patients' age, tumor size, and tumor multicentricity were all significantly related to their gender (p=0.011, p=0.001, and p=0.021, respectively). Further, age, male gender, and tumor size were all significantly related to tumor multicentricity (p=0.003, p=0.021, and p=0.001, respectively). BCC was most commonly found in male, and the diameters of the BCC tumors were also larger in male patients. Multiple BCC was more frequently seen in older and male patients, and the tumors had larger diameters in these groups. The nodular type of BCC was the most frequently seen type in all age groups. CONCLUSION: As our study is the first BCC study that has the greatest number of cases in Turkey and as Istanbul reflects the population of Turkey, it is important for the data of BCC cases in Turkey.

Epiphrenic Diverticulum in an Infant with Congenital Esophageal Stenosis Associated with Esophageal Atresia.

Congenital esophageal stenosis (CES) is a rare congenital disorder which may be isolated or associated with esophageal atresia (EA). It courses with esophageal outflow tract obstruction. Esophageal epiphrenic diverticulae are esophageal outpouchings above diaphragm which develop because of an underlying esophageal motor disorder. We present an infant who had CES associated with EA detected during the course of routine follow-up. She underwent several sessions of esophageal balloon dilatations for CES with some symptomatic improvement. However, an epiphrenic diverticulum (ED) developed during the course of treatment which was detected by further investigations. A surgical excision was performed with a successful outcome. An ED developed secondary to CES has not been previously reported. We have highlighted the diagnostic modalities employed, treatment options, and clinical follow-up for these two rare conditions in children.

Diagnostic accuracy of molecular testing with three molecular markers on thyroid fine-needle aspiration cytology with abnormal category.

BACKGROUND: Cases with abnormal category, determined by thyroid fine-needle aspiration (FNA), frequently undergo surgical resection, despite the majority of cases being identified as benign after resection. Additional diagnostic markers are needed to guide the management of patients with abnormal thyroid nodules. MATERIALS AND METHODS: The retrospective study enrolled 150 cases diagnosed abnormal by FNA cytology that had undergone molecular testing with three markers (BRAF V600E, NRAS, and KRAS) on the cell block. Seventy-one cases had a surgical follow-up. RESULTS: When NIFTP is not considered as malignant, positive predictive values (PPVs) of cytology and combined cytology and molecular testing (CC-MT) were 67.6% (95% CI: 0.555-0.782) and 89.2% (95% CI: 0.746-0.970) (P = .004), respectively. The sensitivity of the CC-MT was 68.8%, specificity was 82.5%, and the false-positive rate was 17.4%. When NIFTP is considered as malignant, PPVs of cytology and CC-MT were 83.1% (95% CI: 0.743-0.918) and 94.6% (95% CI: 0.873-1.018) (P = .047), respectively. The sensitivity of the CC-MT was 59.3%, specificity was 83.3%, and the false-positive rate was 16.7%. CONCLUSION: The addition of molecular testing with a small panel to FNA cytology may increase the PPV of cytology in abnormal categories. Small panel (BRAF V600E, KRAS, and NRAS) with high specificity and high PPVs may be used particularly for the detection of thyroid malignancy. Cell blocks can be an especially useful and straightforward method for molecular diagnostic studies.

Determining the cut-off values of tumor diameter, degree of extraprostatic extension, and extent of surgical margin positivity with regard to biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: The pre-biopsy (bx) prostate-specific antigen (PSA) level, tumor volume/diameter, degree of extraprostatic extension (EPE), and extent of surgical margin positivity have been shown to be significant prognostic parameters of biochemical recurrence (BCR) after radical prostatectomy. The present study assessed the cut-off values of the pre-bx PSA level, maximum tumor diameter, radial and circumferential distances of EPE, and circumferential length of surgical margin (SM) positivity with regard to BCR. MATERIAL AND METHODS: The study included 445 radical prostatectomy specimens, and the cut-off values of all parameters were determined using receiver operating characteristic curve analysis. RESULTS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm were identified as independent predictors of BCR after radical prostatectomy. The parameters that showed statistical significance in univariate analysis, such as pre-bx PSA level ≥ 7.20 ng/mL, tumor diameter ≥ 19.5 mm, presence of seminal vesicle invasion, and circumferential distance of EPE >3 mm, did not have independent prognostic values for BCR. CONCLUSIONS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm are predictors of BCR. Our findings might have significance in risk classification and adjuvant therapy consideration among patients with localized prostate cancer.

Prevalence of high-risk human papilloma virus in liquid-based cervical samples from Turkish women with normal and abnormal cytology.

BACKGROUND: The aim of this study was to investigate the prevalence of human papilloma virus (HPV) infection from Turkish women with normal and abnormal cytology. METHODS: Our study population consisted of 1252 women with normal and abnormal cytology. In our clinic, cervical cancer screening was performed by liquid-based cytology testing (ThinPrep Pap Test). Reflex high-risk (HR) HPV testing (Cervista HPV HR and HPV 16/18) was performed in cases with abnormal cytology (n = 330). HR HPV testing was performed to 922 cases with normal cytology. RESULTS: HR HPV was detected in 18.7% of negative for intraepithelial lesion or malignancy (NILM) samples, and in 79.7% of abnormal cytology cases. HPV types 16 and/or 18 were found in 18.6% and 35.3% of normal cytology cases and abnormal cytology cases, respectively. Of all 435 HR HPV-positive samples, HPV type 16 and/or 18 prevalence was significantly higher in cases with more severe cytological abnormalities. CONCLUSIONS: The HPV prevalence among Turkish women with normal and abnormal cytology identified in this study largely concurs with those in other studies throughout the world. HPV types 16 and/or 18 were detected significantly in normal cytology cases in our study. We also found that, as has been previously demonstrated, certain HPV genotypes (16/18) are associated with more severe pathologies. However, larger epidemiological studies in different regions of Turkey are needed to evaluate the accurate prevalence of HPV infection throughout the country.

Evaluation of the Effect of Topical Application of Nigella sativa on Acute Radiation-Induced Nasal Mucositis.

The goal of this study was to demonstrate the effect of radiotherapy (RT) on nasal mucosa in rats and to evaluate the radioprotective effects of the topical application of black seed oil (Nigella sativa [NS]) to treat acute radiation-induced nasal mucositis.A total of 18 rats were randomized into 3 groups, with 6 animals per group. The rats in group 1 were topically administered saline in the nasal cavity after sham irradiation. Group 2 received saline at the same dose after irradiation. Group 3 was given NS after irradiation. The rats in groups 2 and 3 were irradiated with a single dose of 40 Gy to the nasal and paranasal area. Only one drop of saline (0.05 mL) was applied to each nostril in the first, second, and third days after RT in groups 1 and 2. One drop of cold press NS (0.05 mL) was applied to each nostril in group 3. Fourteen days after irradiation, the nasal mucosal tissues were excised for histopathological evaluation. Vascular dilatation, inflammatory cell infiltration, superficial erosion, and formation of exudates were classified according to the severity.No evidence of mucositis was observed in group 1. Of all the parameters the only statistically significant difference between groups 2 and 3 were observed for "superficial erosion' (P < 0.05). Overall microscopic observations in the NS-treated group were better than in group 2.The preliminary results of our study have shown that local application of NS to the nasal mucosa may be an effective treatment of acute nasal mucositis due to RT.

The clinical performance of computer-assisted liquid-based cytology, primary hrHPV screening, and cotesting at a Turkish Tertiary Care Hospital.

BACKGROUND: We aimed to compare the performance of computer-assisted liquid-based cytology, primary high-risk human papillomavirus (hrHPV) screening, and cytology-hrHPV cotesting with regards to the detection rate of cervical cancer precursor lesions. METHODS: A total of 22,653 computer-assisted liquid-based cytology specimens interpreted between 2013 and 2015 were included in the study. We compared the false-negative rates and sensitivities for computer-assisted liquid-based cytology, primary hrHPV screening and cytology-hrHPV cotesting among women with normal and abnormal cytologies. Among 1,748 women who had undergone cotesting, 249 underwent follow-up biopsies. RESULTS: For detecting biopsy-confirmed high-grade lesions, the sensitivities of using hrHPV, Pap tests, and cytology-hrHPV cotesting were 90.67%, 88%, and 98.67%, respectively, while the false-negative rates for hrHPV and Pap tests were 9.3% and 12%, respectively. The false negative rate for cotesting was only 1.3%. CONCLUSION: Based on the significantly high sensitivity and lower false-negative rates achieved, we conclude that the combination of cytologic screening with hrHPV testing is the best preferred strategy for detection of cervical precursor lesions in our country's conditions.

The significance of parakeratosis alone in cervicovaginal cytology of turkish women.

BACKGROUND: We aimed to analyze the significance of parakeratosis on an otherwise negative Papanicalaou (Pap) smear, in the absence of any characteristic human papilloma virus (HPV) findings. METHODS: A total of 22,076 Papanicalaou smears that were diagnosed as negative for intraepithelial lesions or malignancy between 2013 and 2015 were included in this study. Samples were separated into two groups, according to the presence of parakeratosis. We investigated the association between parakeratosis in the cytology results and a high-risk HPV status and high-grade squamous intraepithelial lesion (HSIL) in the colposcopic biopsy specimens. RESULTS: A positive HPV result was more frequently identified in cases with parakeratosis than in cases without parakeratosis (P < 0.001). A histological diagnosis of HSIL was more frequently observed in HPV-positive cases with a diagnosis of parakeratosis on cytology than in cases without parakeratosis (P = 0.8). CONCLUSION: Our results demonstrate that a finding of parakeratosis on an otherwise negative Pap smear supports a follow-up HPV DNA test. Also we should consider whether the presence of parakeratosis should be included in standard cytology reports. Additionally parakeratosis trended toward increased frequency of HSIL in follow-up biopsy specimens. But it did not reach statistical significance. That is why larger studies are necessary to evaluate the association of parakeratosis and HSIL in colposcopic biopsy specimens. Diagn. Cytopathol. 2017;45:297-302. © 2016 Wiley Periodicals, Inc.

Outcomes of Gleason score 3 + 4 = 7 prostate cancer with minimal amounts (<6%) vs ≥6% of Gleason pattern 4 tissue in needle biopsy specimens.

OBJECTIVE: The International Society of Urological Pathology Gleason grading system was modified in 2005. Since the modified system was introduced, many cancers that previously would have been categorized as Gleason score (GS) 6 are now categorized as GS 7 based on biopsy specimens that only contain minimal amounts (<6%) of Gleason pattern (GP) 4 tissue. However, the clinical significance of observing <6% of GP 4 tissue in biopsies of GS 7 prostate cancer has not been studied. MATERIAL AND METHODS: This study was based on needle biopsy specimens that were categorized as GS 6 or GS 7 and were obtained from patients who underwent radical prostatectomy (RP) with available follow-up data. We assessed the quantity of GP 4 tissue in biopsy specimens of GS 7 prostate cancer. Further, we evaluated the correlation between the quantity of GP 4 tissue and disease progression after RP. RESULTS: GP 4 comprising 26-49% of the specimen, GS 4+3 and percentage of total core tissue scored as positive were significant and independent predictors of prostate-specific antigen (PSA) failure after RP, as assessed using a multivariate Cox regression model that included the quantity of GP 4 in the prostate biopsy specimen, preoperative PSA, perineural invasion, clinical stage, number of positive cores, and percentage of core tissue scored as positive. Cases with GS 3+3 and cases in which the observed GP 4 area was <6% did not differ significantly in terms of biochemical PSA recurrence (BPR) status. In contrast, cases with 6-25% GP 4 tissue, 26-49% GP 4 tissue, and GS 4+3 showed more frequent BPR than cases with GS 3+3. CONCLUSIONS: Our data suggest that the quantity of GP 4 tissue in GS 7 cancer has clinical significance. However, there is a need for larger studies of the clinical significance of biopsy specimens that include <6% GP 4 tissue. We should reconsider whether the amount of GP 4 should be included in standart pathology reports.