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Milena Taskovska,1 Maja Frelih,2 Tomaž Smrkolj,1 Metka Volavšek2 1Chair of Surgery, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; 2Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, SloveniaCorrespondence: Metka Volavšek; Milena Taskovska, Email metka.volavsek@mf.uni-lj.si; milena.taskovska@kclj.siPurpose: Basal cell carcinoma of the prostate is rare. Usually, it is diagnosed in elderly men with nocturia, urgency, lower urinary tract obstruction and normal PSA.Case Presentation: We report on a case of a 56-years-old patient who presented at the emergency ward with weight loss, nausea and vomiting. The diagnostic evaluation showed acute renal failure due to a bladder tumor. After admission to the urology ward and subsequent contrast-enhanced CT urography and contrast-enhanced chest CT, a non-metastatic bladder tumor that infiltrated the right side of the bladder and seminal vesicles was found. High-grade muscle-invasive urothelial carcinoma was diagnosed from TURBT specimens, followed by radical cystoprostatectomy with pelvic lymphadenectomy and formation of ureterocutaneostomy sec. Bricker. The histopathological examination of the resection specimen surprisingly revealed the presence of prostatic basal cell carcinoma pT4N0M0 and not urothelial cancer. Due to renal failure, the patient required hemodialysis. The recommendation of the multidisciplinary oncological meeting was to follow up with the patient by the surgeon-urologist. On imaging six months after surgery, it was suspicious for recurrence. Patient was considered for adjuvant oncological treatment.Conclusion: Although rare, basal cell carcinoma of the prostate should be considered in patients with lower urinary tract symptoms, hematuria and normal PSA. Transurethral resection of bladder tumor is indicated in patients presenting with hematuria and bladder tumor. In evaluation of such cases rare histological types should be included in the differential diagnosis.Keywords: prostate cancer, basal cell carcinoma of the prostate, renal failure, bladder tumor, transurethral resection of bladder tumor, cystoprostatectomy

Abstract Background Despite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development. Methods We used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the KRAS mutation was investigated. Results We detected significant previously undescribed underexpression in CRC for genes SLC26A3, TPM1 and DCN, with a suggested tumour suppressor role. We also describe the correlation between TPM1 and DCN expression and the presence of KRAS mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the TPM1 gene in one case of CRC, but no deletions of DCN and SLC26A3 were found. Conclusion Our study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the TPM1 gene in a case of CRCs without KRAS mutations, showing that TPM1 might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the TPM1 gene. On the other hand, the correlation of DCN underexpression with the presence of KRAS mutations suggests that DCN expression is affected by the presence of activating KRAS mutations, lowering the amount of the important tumour suppressor protein decorin.

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates., (© 2024. The Author(s).)

Purpose: Post prostatectomy PSA kinetics and General Grade Groups (GGG) are the strongest prognostic markers of biochemical recurrence (BCR) and prostate cancer (PCa)-specific mortality after radical prostatectomy. Despite having low-risk PCa, some patients will experience BCR, for some, clinically significant BCR. There is a need for an objective prognostic marker at the time of prostatectomy to improve risk stratification within this population. In this study, we investigated the prognostic potential of DNA ploidy., Materials and Methods: Prostatectomy samples from 97 patients with GGG1 and GGG2 with a low-risk CAPRA-S score were included in this study. PCa tissue with the worst Gleason pattern underwent tissue disaggregation, cell isolation and staining with a DNA stoichiometric stain. Using image cytometry, DNA ploidy was measured and a Ploidy Score (PS) was generated., Results: Among the 97 patients, 79 had no BCR, 18 experienced BCR, of which 14 had a PSA doubling time (PSA-DT) >1 year (low-risk group) and 4 had a PSA-DT of <1 year (high-risk group). Using Logistic regression analysis, only pathological T stage (pT) and PS independently predicted BCR with PS being the most significant (p = 0.001). The number of aneuploid cells was significantly higher in the high-risk group compared to the other groups (p = 1.7x10-11). PS combined with GGG diagnosis further stratified risk groups of biochemical recurrence free survival within CAPRA-S low-risk cohort., Conclusion: DNA ploidy is an independent prognostic marker of BCR in low-risk PCa after radical prostatectomy, which could early on identify potentially aggressive PCa recurrences and introduce a more personalized approach to salvage treatments.

The aim of the study was to stratify high-grade T1 (HGT1) bladder urothelial carcinoma into risk categories based on the presence of variant histology when compared to conventional urothelial carcinoma. The clinicopathological features of 104 HGT1 cases of urothelial carcinoma of the bladder with variant histology present in 34 (37%) were assessed. The endpoint of the study was disease-free survival and cancer-specific survival. Overall, variant histology was identified as a significant predictor of disease-free survival (P = 0.035). The presence of any specific variant histology (squamous, glandular, micropapillary, nested, microcystic, inverted growth, villous-like, basaloid, and lymphoepithelioma-like) was identified as a significant predictor of disease-free survival (P = 0.008) and cancer-specific survival (P = 0.0001) in HGT1 bladder cancer. Therefore, our results support including micropapillary HGT1 urothelial carcinoma within the aggressive high-risk category, as suggested by some recent clinical guidelines, but also favor nested, glandular, and basaloid to be placed in the high-risk category due to their potential of aggressive, life-threatening behavior and their limited response to bacillus Calmette-Guerin therapy. Conversely, the low-risk category would include urothelial carcinomas with squamous, inverted growth, or microcystic morphology, all with limited life-threatening potential and good response to current therapy. A very low-risk category would finally include patients whose tumors present villous-like or lymphoepithelioma-like morphology. In conclusion, our findings support the value of reporting the variant histology as a feature of variable aggressiveness in HGT1 urothelial carcinoma of the bladder., (© 2022. The Author(s).)

Aims: The transcriptional activity of high-risk human papillomaviruses (HR-HPV) within oropharyngeal squamous cell carcinomas (OPSCC) has been linked to improved survival of patients. HR-HPV mRNA silver in situ hybridization (SISH) was evaluated on a cohort of OPSCC and compared with viral HPV DNA tests and p16 expression. Clinical outcomes of HPV-driven OPSCC and non-HPV related OPSCC were also studied., Methods: We evaluated 67 OPSCC and 3 papillomas, obtained from 62 patients, for detection of HR-HPV DNA by PCR tests. The positive samples were additionally studied by the SISH method using three probes of HPV16, HPV18, and HP33, and for p16 expression detected by immunohistochemistry. SISH assays were evaluated for the presence/number and intensity of signals in cancer cells. Prognostic significance of HPV status in our cohort was evaluated with univariate and multivariate statistics., Results: According to the HR-HPV PCR tests, 46 (69%) OPSCC cases were HPV positive, while three papillomas were negative. Of total 46 HPV-positive OPSCCs, 43 cases were also SISH-positive, while p16 overexpression was found in 45 of 46 HPV positive OPSCC cases. In OPSCC specimens, the sensitivity and specificity of the combined SISH probes (HPV16 and 33) were both 100.00%, when compared to HPV PCR. HPV positivity of the tumors appeared significant for predicting progression-free survival, cause specific survival and overall survival in a multivariate setting., Conclusions: The recently developed mRNA SISH methodology can detect HPV-driven OPSCCs without any additional test in 79% of cases. Positive SISH signals enable the visualization of viral transcripts required to recognize clinically relevant HPV infection. However, rare and tiny signals require an experienced pathologist to establish a consensus interpretation of results. The currently applied HR-HPV mRNA SISH analysis may serve as a groundwork for additional studies., (Copyright © 2021 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Purpose: Prostate cancer (PCa) with biopsy-based grade group (GG) 1 or 2 characteristics has a favorable outcome, yet some cases still progress after radical prostatectomy and present with biochemical recurrence (BCR). We hypothesized that the multi-scale tissue architecture (MSTA) analysis score would correlate with the aggressive PCa phenotype and could be used as a tool for risk assessment to improve the management of patients with favorable-risk PCa., Materials and Methods: MSTA was evaluated in needle-biopsy samples from 115 patients with favorable-risk PCa, as defined by GG1 and GG2, a prostate-specific antigen (PSA) level of <10 ng/mL, a clinical stage of cT1c to cT2b, and general Gleason GG (GGG) and expert pathologist-assessed GG (EGG). Algorithms based on Voronoi diagrams were applied to all Feulgen-thionin-stained diagnostic areas. One hundred tissue architecture features were calculated and an MSTA score, a linear combination of the most discriminant features, was generated. Correlation of MSTA score with BCR and other clinical variables was investigated., Results: In a univariate regression model, EGG, clinical stage, and MSTA were significant predictors of BCR (respective p-values: 0.0016, 0.016, and 0.028). Survival analysis showed that patients with a high MSTA score were more likely to experience BCR than were patients with a low MSTA score (odds ratio, 2.9). Combining MSTA with GG assessment resulted in a significant stratification of risk for BCR., Conclusions: MSTA score could be used as an objective adjunct risk stratification tool to pathologist assessments and could improve the management of patients with favorable-risk PCa., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2020.)

We report on the clinicopathologic features of 115 cases of high-grade urothelial carcinoma of the upper urinary tract with variant histology present in 39 (34%). Variant histology was typically seen in high pathological stage (pT2-pT4) (82%, 32 cases) patients with lower survival rate (70%, 27 cases, median survival 31 months) and consisted in urothelial with one (23%), two (3%), and three or more variants (3%); 4% of cases presented with pure variant histology. Squamous divergent differentiation was the most common variant (7%) followed by sarcomatoid (6%) and glandular (4%), followed by 3% each of micropapillary, diffuse-plasmacytoid, inverted growth, clear cell glycogenic, or lipid-rich. The pseudo-angiosarcomatous variant is seen in 2%, and 1% each of nested, giant-cell, lymphoepithelioma-like, small-cell, trophoblastic, rhabdoid, microcystic, lymphoid-rich stroma, or myxoid stroma/chordoid completed the study series. Loss of mismatch repair protein expression was identified in one case of upper urinary tract carcinoma with inverted growth variant (3.6%). Variant histology was associated to pathological stage (p = 0.007) and survival status (p = 0.039). The univariate survival analysis identified variant histology as a feature of lower recurrence-free survival (p = 0.046). Our findings suggest that variant histology is a feature of aggressiveness in urothelial carcinoma of the upper urinary tract worth it to be reported.

Focal or non-focal/extensive extraprostatic extension of prostate carcinoma is an important pathologic prognostic parameter to be reported after radical prostatectomy. Currently, there is no agreement on how to measure and what are the best cutoff points to be used in practice. We hypothesized that digital microscopy would potentially provide more objective measurements of extraprostatic extension, thus better defining its clinical significance. To further our knowledge on digital prostate pathology, we evaluated the status of extraprostatic extension in 107 consecutive laparoscopic radical prostatectomy samples, using digital and conventional light microscopy. Mean linear and radial measurements of extraprostatic extension by digital microscopy significantly correlated to pT status (p = 0.022 and p = 0.050, respectively) but only radial measurements correlated to biochemical recurrence (p = 0.042) and grade groups (p = 0.022). None of the measurements, whether conventional or digital, were associated with lymph node status. Receiving operating characteristic analysis showed a potential cutoff point to assess linear measurements by conventional (< vs. > 24.21 mm) or digital microscopy (< vs. > 15 mm) or by radial measurement (< vs. > 1.6 mm). Finally, we observed an association between the number of paraffin blocks bearing EPE with pT (p = 0.041) status (digital microscopy), and linear measurements by conventional (p = 0.044) or digital microscopy (p = 0.045) with lymph node status. Reporting EPE measurements by digital microscopy, both linear and radial, and the number of paraffin blocks with EPE, might provide additional prognostic features after radical prostatectomy.

Drugs for the treatment of depressive disorders, including SNRIs (serotonin noradrenaline reuptake inhibitors) venlafaxine and duloxetine, are widely prescribed as they have a high therapeutic to toxicity ratio. In rare cases, adverse effects may be severe, usually due to iatrogenic, accidental or intentional self-overdose that cause the excessive accumulation of serotonin and noradrenaline in synaptic clefts. Lethal intoxication with a combination of venlafaxine and duloxetine (postmortem blood concentrations 24 mg/L and 0.97 mg/L, respectively) without co-ingested substances, comorbidities or injuries that could have an unknown contribution to a fatal outcome is presented for the first time in the following case report, with a comprehensive clinical history, and complete results of the performed analyses. The cause of death was a serotonin syndrome that progressed to death in approximately six hours and 15 min after the suicidal ingestion of venlafaxine and duloxetine. Despite the high therapeutic to toxicity ratio SNRIs, which are reserved for patients with severe forms of depressive disorders and a higher suicidal tendency, they should be cautiously prescribed and handed over in smaller packages to make them easier to follow, and thus avoid accumulation within the patient's reach.

Positive surgical margin (PSM) extension reported as focal or non-focal/extensive is an important pathologic prognostic parameter after radical prostatectomy. Likewise, there is limited or no agreement on how to measure and what the best cut-off points to be used in practice are. We hypothesized that digital microscopy (DM) would potentially provide a more objective way to measure PSM and better define its clinical significance. To further our knowledge, we have evaluated PSM status in 107 laparoscopic radical prostatectomies using digital and conventional light microscopy (LM). DM evaluation detected three additional PSM cases, but no differences were seen (LM vs DM; p = 0.220). Mean linear measurement correlated to biochemical recurrence (BR) (LM, p = 0.002; DM, p = 0.001). ROC analysis identified a cut-off point to assess linear measurement by LM (3.5 mm) or DM (3.2 mm), but only digital measurement was significant for BR-free survival. Our study also evaluated a cut-off ≤ 3 mm that was associated to BR using LM (p = 0.023) or DM (p = 0.001). Finally, the number of paraffin blocks bearing PSM correlated with BR (p < 0.001) status with either LM or DM. In conclusion, DM produces similar data than LM but shows more accurate measurements. Reporting of PSM with score of ≤ 3 vs. > 3 mm linear extent using LM (3.2 mm if digital microscopy is applied) might represent an important prognostic feature after radical prostatectomy. Alternatively, reporting the number of blocks with PSM 1 vs. 2 or more might also provide important prognostic data in practice.

Malignant salivary gland tumours are rare histologically and clinically heterogeneous group of tumours, missing prognostic factors and therapeutic targets. MicroRNAs (miRNAs), small noncoding RNAs, and posttranscriptional regulators of mRNA are poorly described in different subtypes of salivary gland tumours. Epidermal growth factor receptor (EGFR), an important therapeutic target and target of certain miRNAs (i.e., miR-133b ), shows variable degrees of expression in salivary gland tumours. Our study included 70 parotid gland tumours of different histological subtypes. Expression, mutations, and copy number variations (CNVs) of EGFR were determined using immunohistochemistry, single-stranded conformation polymorphism, quantitative polymerase chain reaction (qPCR), and fluorescence in situ hybridization. Expression of miR-99b , miR-133b , miR-140 , miR-140-3p , and let-7a was analysed using qPCR. Expression of EGFR was observed in 37% of tumours with low and 40% of tumours with high malignant potential. There were no mutations, with the majority of samples showing polysomy of chromosome 7. Based on histological subtypes, we found differential expression of all five miRNAs. We confirmed association of reactivity of EGFR, miR-133b , miR-140 , miR-140-3p , and let-7a with CNV of EGFR and a positive association between miR-133b / let-7a and reactivity of EGFR. Age and need for postoperative radiotherapy were characterized as significant in multivariate survival analysis., Competing Interests: The authors declare that they have no competing interests.

Mixed acinar-ductal carcinoma is rare among pancreatic cancers, as is duodenal involvement in follicular lymphoma (FL). Although usually a systemic disease, primary FL of the duodenum occurs, with superficial involvement of the intestinal wall and low risk of progression. We report on a unique case of mixed ductal-acinar carcinoma of the pancreatic head accompanied by low-grade duodenal FL and autoimmune pancreatitis-like changes in adjacent pancreatic parenchyma. To our knowledge this is the first report of concomitant pancreatic mixed acinar-ductal carcinoma and duodenal FL. Clinico-pathological features of this unusual case, possible relationship between the entities and differential diagnosis are discussed.

Reported prostate cancer incidence rates vary greatly among cystoprostatectomy samples. We investigated how the thoroughness of prostate sampling influences prostatic carcinoma incidence in bladder cancer patients. In a retrospective study, 313 cystoprostatectomy cases of urinary bladder carcinoma were analysed for the presence of concurrent prostatic carcinoma. Patients were divided into two groups: patients who had undergone the operation before and after 2007, when a policy of preferably complete prostate sampling in cystoprostatectomy specimens was introduced at our institution. Cases processed after the 2007 recommended sampling changes had a significantly higher rate of incidental prostatic carcinoma and clinically significant prostatic carcinoma than the pre-2007 group (p < 0.0001 and p = 0.003, respectively). Complete prostate processing in cystoprostatectomy specimens results in a higher incidence of incidental prostatic carcinoma than with partial processing. More patients with clinically significant prostate cancer are consequently discovered. In conclusion, we believe that complete prostate sampling should be mandatory.

Laryngeal carcinogenesis is a multistep process, characterized by an accumulation of genetic changes associated with architectural and cytologic alterations, ranging from squamous hyperplasia to carcinoma in situ and encompassed by the terminology of squamous intraepithelial lesions (SILs). The etiology, classification, genetic changes, and malignant progression of these lesions are reviewed. Tobacco remains the principal etiological factor with gastroesophageal reflux disease recently considered as a possible factor. In contrast, there is little evidence that microbiological agents, especially human papillomavirus infection, are frequently involved in laryngeal carcinogenesis and probably <10% of SILs are driven by biologically active human papillomavirus infection. Light microscopy, despite a degree of subjectivity, remains the mainstay of accurate diagnosis, prognosis, and guidance for a patient's treatment. The currently used classifications, the dysplasia system, squamous intraepithelial neoplasia, and the Ljubljana classification, reflect different standpoints on this important topic. The modified Ljubljana classification, with good interobserver agreement, could be considered as a proposal for a unified classification of laryngeal SILs. This review also briefly discusses recently discovered genetic changes, such as CDKN2A and CTNNB1 genes, and chromosome instability of chromosomes 1 and 7; however, none of these can at present improve histologic diagnosis. Malignant progression of precursor lesions varies from 2% to 74%, according to different studies. Cold-steel microinstruments, CO2 laser, and radiotherapy are used to treat the different grades of precursor lesions. There is as yet no worldwide agreement on the treatment of high-grade lesions and carcinoma in situ.

Background: Uromodulin, also known as Tamm-Horsfall glycoprotein (THG), is the most abundantly produced protein appearing in normal urine. Under normal conditions it has several functions, the most important being the provision of a water-tight boundary to the end path of filtration and the prevention of urinary tract infections. Under certain conditions THG is accumulated in urinary tract organs and the deposition is most often clinically silent., Case: We report a case of 78-year-old man with clinically evident hydronephrosis and stenosis of the right ureter. Clinically, a neoplasm was suspected. Histological examination of ureter tissue revealed abundant deposits of THG in the ureter wall without any inflammatory reaction., Conclusion: In cases with deposition of eosinophilic material in the urinary tract organs, accumulation of THG should be considered in the differential diagnosis. To our knowledge this is the first report of tumor-like accumulation of THG in the ureter.

Nonsurgical therapeutic options for prostatic diseases are divided into androgen action-related, with androgen action inhibition (AAI), or androgen action-unrelated strategies, such as radiotherapy (RT). AAI, achieved by numerous medications with antiandrogen activity, is used for prostatic hyperplasia and carcinoma. Treatment mostly affects secretory epithelial cells, with consequent reduction in prostate volume and diminished amount of cancer. Histologically, AAI changes the morphologic appearance of benign prostatic glands, prostatic intraepithelial neoplasia, and cancer, as well as prostatic stroma. The effects of most AAI drugs are similar, although variable in intensity. Expression of some diagnostic immunohistochemical markers can decline after longtime treatment, requiring careful interpretation of staining results. Patterns of tissue injury after RT for prostate cancer differ from those after AAI. While irradiation has a profound effect on benign prostatic glands, it does not affect immunohistochemistry, which retains its diagnostic value. In order to make a reliable diagnosis in needle biopsies of treated prostate cancer, uropathologists should have all the relevant information on treatment modalities and their duration. As treatment affects the morphology of prostate cancer, Gleason grading is unreliable and therefore not recommended. An overview of treatment effects caused by AAI and RT is herein presented, with discussion on their importance in everyday practice.

Aims: To verify the applicability, reproducibility and predictive value of a proposed unified classification (amended Ljubljana classification) for laryngeal squamous intraepithelial lesions (SILs)., Methods and Results: Six internationally recognized experts and three pathologists from Ljubljana contributed to this study by evaluating a set of laryngeal SILs using the new system: low-grade SIL, high-grade SIL, and carcinoma in situ (CIS). The overall agreement among reviewers was good. Overall unweighted and weighted κ-values and 95% confidence intervals were 0.75 (0.65-0.84) and 0.80 (0.71-0.87), respectively. The results were stratified between the international reviewers and the Ljubljana pathologists. The former had good overall agreement, and the latter had very good agreement. Kaplan-Meier survival curves showed a significant difference (P < 0.0001) between patients with low-grade and high-grade SILs; 19 of 1204 patients with low-grade SILs and 30 of 240 patients with high-grade SILs progressed to malignancy in 2-15 years and in 2-26 years, respectively., Conclusions: The proposed modification to the Ljubljana classification provides clear morphological criteria for defining the prognostic groups. The criteria facilitate better interobserver agreement than previous systems, and the retrospective follow-up study demonstrates a highly significant difference in the risk of malignant progression between low-grade and high-grade SILs., (© 2014 John Wiley & Sons Ltd.)

Thyroid-like follicular carcinoma of the kidney (TLFC), a rare neoplasm with low malignant potential, is histologically similar to primary thyroid follicular carcinoma, but characteristically lacks thyroid immunohistochemical markers. We report a case of 34-year old patient with nephrolithiasis. Ultrasound revealed hepatorenal cysts consistent with adult type polycystic kidney disease (ATPKD) and a cytologically confirmed left kidney tumor. Nephrectomy specimen contained sharply demarcated lesion of unusual morphology. Tubular and cystic structures lined by mostly cuboidal cells and filled with amorphous eosinophillic material, reminiscent of follicular carcinoma of the thyroid gland, were diagnostic for TLFC. Thyroid markers were negative. To our knowledge this is the first report of TFLC associated to ATPKD. Brief review of previously published TFLCs, possible relationship between entities and differential diagnosis are discussed., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8067946569612694.

The study focuses on BBC3 gene expression in primary head and neck squamous cell carcinomas (HNSCC) in relation to pTNM classification. We used quantitative real-time PCR on 35 biopsy samples of HNSCC tumor samples to evaluate differences of BBC3 expression depending on tumor size, regional lymph node involvement, location and tumor staging. In order to confirm the model of BBC3-mediated apoptosis, we used immunohistochemistry to determine the expression of apoptotic proteins p53, p63, Bcl-2 and Bax. We also used publicly available cDNA microarray datasets. Our results show a general down-regulation of BBC3 in tumor tissue compared to adjacent normal tissue. The expression was significantly altered among different groups of patho-histologically evaluated tumor sizes, but not in relation to tumor location, regional lymph node involvement or tumor stage. That suggests the potential use of BBC3 as a new tumor size marker in HNSCC. Through protein expression analysis combined with publicly available cDNA microarray datasets of apoptotic factors, we confirmed the model of BBC3-mediated apoptosis, which can be activated with or without p53.