Risk for testicular germ cell tumors and spermatogenesis failure in post-pubertal undescended testes.

PURPOSE: Cryptorchidism is a well-defined risk factor for testicular germ cell tumors, whereas the underlying mechanisms have not been fully elucidated. Surgical procedures to reposition undescended testicles into the scrotum (orchidopexy) in early childhood are recommended both to increase fertility potential and to reduce the risk of developing testicular tumors. However, treatment in the post-pubertal period is controversial. The aim of this study is to review the histopathology of orchiectomy specimens and determination of spermatogenesis in post-pubertal patients with non-treated cryptorchidism. METHODS: Retrospective chart review was performed to assess the occurrence of TGCTs and determine spermatogenesis in post-pubertal individuals who underwent inguinal orchiectomy for undescended testis between January 2010 and December 2019. Age at the time of surgery, laterality, location of the undescended testis and pathology results were evaluated. All pathology specimens were reviewed by a blinded pathologist. RESULTS: There were 23 patients in the cohort with a mean age of 21 years (range 13-46 years). All testes were in the inguinal canal. Our results indicated that 1 patient had seminoma. In the histological evaluation of the remaining 22 patients in whom no tumor was detected, normal spermatogenesis was not observed in any patient. Further, seminiferous tubules were not found in 19 patients. Maturation arrest was detected in the remaining 3 patients. CONCLUSION: Testicular germ cell carcinoma was found in 4% of the patients who underwent post-pubertal orchiectomy. In addition, none of the undescended testes had normal spermatogenetic activity. Thus, orchiectomy should be considered in post-pubertal males with unilateral undescended testis that do not need the endocrinological activity of the testis.

The findings of impacted and transmigrated maxillary and mandibular canines: a retrospective cone beam computed tomography study.

BACKGROUND: The aim of this study was to examine and evaluate the maxillary and mandibular impacted and transmigrant canines, their relationship with neighboring tissues and pathology with cone beam computed tomography (CBCT). METHODS: CBCT data of 217 patients, between January 2018 and December 2019, with a total of 293 impacted canines were retrospectively reviewed. Clinical records were also evaluated. Maxillary or mandibular localization, angulations, transmigration, lateral and premolar tooth resorption, apical dilacerations, pathological formations, presence of persistent deciduous canines and treatment methods were investigated. RESULTS: For 293 impacted canines, 237 were in the maxilla and 56 in the mandible, with this difference being statistically significant (P<0.05). Among the 293 impacted canines, 14 (4.8%) transmigrated canines were detected. From the 14 transmigrant canines, 13 were in the mandible and 1 was in the maxilla. This difference was found statistically significant (P<0.05). Eighteen dentigerous cysts (10 maxilla, 8 mandible) and 4 odontomas (3 maxilla, 1 mandible) were found in impacted canines. For a total of 293 impacted canines, 57 were extracted, 13 were referred to orthodontics and a follow-up decision was made for 223 teeth. CONCLUSIONS: Transmigration incidence is statistically significant, on a higher area of the lower jaw, compared to the upper jaw (P<0.05). In patients with impacted canines, taking CBCT together with a detailed clinical examination is effective in correct treatment planning and in minimizing complications that may occur during surgical extraction.

The statuses of HER2 expression and mismatch repair in endometrial clear cell carcinoma.

High-grade endometrial carcinomas (HGEC) are difficult to classify. With the current use of HER2-based therapy in serous carcinoma, a diagnosis of clear cell carcinoma (CCC) has the potential to exclude patients from receiving therapy. Therefore, we examined HER2 expression in our CCC patients. The preparations of 8 patients with CCC who underwent hysterectomy, bilateral salpingo-oophorectomy, and lymph node dissection were re-evaluated. Patients did not have any prior treatment. Histopathologic parameters that were evaluated include cytoplasmic clearing, nuclear atypia, mitotic activity, hobnail architecture, hyalinized cores, hyaline globules, stratification of epithelial lining papillae, or glandular structures, and highly atypical cell layers. Immunohistochemically, HER2, ER, PR, HNF1ß, Napsin A, MLH1, MSH2, MSH6 and PMS2 were applied. HER2 staining pattern, ASCO/CAP protocol used for endometrial carcinom was used. HER2 was positive in 3 of our 8 CCC patients (37.5%). While all of our HER2 + cases were Napsin A and HNF1ß positive, MMR proteins were intact and ER and PR were negative. Two patients had wild type p53 and 1 patient had aberrant p53 staining. Considering that there is not always a consensus between SC and CCC, even among gynecopathologists, tumor heterogeneity and different tumor components may exist, and while patients may be diagnosed with CCC and benefit from HER2 therapy, there is also a possibility that they may not benefit from the treatment. The fact that 37.5% of our CCC cases were HER2 + is a finding with strong implications for the therapeutic approach. As a result of our study, in patients with CCC, if MMR is intact and ER-PR is negative, regardless of the p53 staining pattern, HER2 testing may be an objective screening method for patients who are likely to benefit from HER-targeted therapy. Consequently, patients with a diagnosis of CCC can be candidates for future clinical trials of HER2-targeted therapy.

Classification of high-grade endometrium carcinomas using molecular and immunohistochemical methods.

OBJECTIVES: As a result of the integration of molecular changes into the histological classification of cancers, which increases diagnostic repeatability, the differences between the groups become more prominent and targeted therapies gain significance. The most comprehensive molecular study regarding endometrial carcinomas (EC) is The Cancer Genome Atlas (TCGA) project. According to TCGA, endometrial carcinomas are classified into four molecular prognostic subgroups: copy-number-low/p53-wild-type (p53wt), DNA polymerase epsilon (POLE)-mutated/ultramutated (POLEmt), microsatellite-instability/hypermutated (MSI), and copy-number-high/p53-mutated (p53mt). In this study, we aim to apply the molecular classification to our high-grade endometrial cancer patients, and particularly, to identify our overtreated patients. MATERIAL AND METHODS: Ninety-seven patients diagnosed with high-grade EC in Selcuk University, Faculty of Medicine between 2009-2018 were retrospectively evaluated and classified into four subgroups. Primary outcomes of overall and progression-free survival were evaluated for clinical, pathological, and molecular features. Further, all molecular groups were divided into endometroid and non-endometrioid groups, and disease-free survival (DFS) and overall survival (OS) were investigated across groups. RESULTS: According to molecular classification, 23 patients (23.7%) were assigned to the MSI group, 21 (21.6%) to the POLEmt group, 40 (41.2%) to the p53mt group, and 13 (13.4%) to the p53wt group. Patients' DFS (p = 0.001) and OS rates (p = 0.001) were significantly different according to their molecular classification. The results of our analyses determined that, in the molecular classification of high-grade ECs, the p53mt group had the poorest prognosis and the POLEmt group had the best prognosis. Tumor size, myometrial invasion, lymphovascular space invasion (LVSI), lymph node metastasis, cervical invasion, ovarian invasion and stage showed statistically significant differences based on molecular classification (p < 0.05). CONCLUSIONS: The use of molecular classification in the clinical practice will allow more accurate prognostic prediction and more appropriate treatment planning, particularly as high-grade ECs constitute a heterogenous group with poor prognosis.

Early-onset basal cell carcinoma; wide case series at a single tertiary center in middle Anatolia.

OBJECTIVE: Although basal cell carcinoma (BCC) is prevalent in the older population, it can be rarely seen in younger people. This study aims to investigate the risk factors and characteristics of BCC in young patients. METHODS: Pathology reports in a single tertiary care institution between 2010 and 2020 were retrospectively reviewed. Patients under the age of 35 who were diagnosed with BCC were included for the analysis. Data were gathered from medical records and pathology reports. Demographic characteristics, accompanying pathologies, and clinical findings of these patients were analyzed. RESULTS: There were a total of 32 patients in our cohort. Out of 32 patients, 20 were female and 12 were male. One male patient and five female patients were younger than 18. An accompanying risk factor (Gorlin syndrome, XP, renal transplantation, etc.) was present in six patients. There were no known additional diseases or risk factors in 26 patients. Metastasis and recurrence were not reported in any of our patients. Contrary to the information in the literature, the patients with BCC at a young age were not found more aggressive in our study. CONCLUSION: Contrary to the information in the literature, the patients with BCC at a young age were not found more aggressive in our study. Understanding the risk factors associated with BCC is essential for designing prevention strategies and favoring early diagnosis. Awareness of early-onset BCC aids in early diagnosis and treatment of the disease. Therefore, BCC should be in the differential diagnosis of skin lesions in the young population. In addition, when we encounter early-onset BCC, we should not forget the accompanying risk factors and syndromes.

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation.

BACKGROUND: The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin-the effect we tested against MTX-induced oral mucosal damage-are well known. OBJECTIVE: Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. METHODOLOGY: In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. RESULTS: Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. CONCLUSION: These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Effect of Topical Application and/or Systemic Use of Red Ginseng Extract on Wound Healing in Rats With Experimentally Induced Diabetes.

BACKGROUND: Red ginseng (Rg) is an herbal product that has been used in traditional medicine in Asian and European countries for many years. PURPOSE: To study the effects of Rg extract on wound healing when used systemically, locally, or in combination in rats with experimentally induced diabetes. METHODS: A total of 60 rats were randomly divided into 4 groups: saline (control), local Rg (LRg), systemic Rg (SRg), and local + systemic = combined Rg (CRg). A full-thickness wound (2 cm × 1 cm) was created on the back of the rats, and treatment protocols were carried out for 14 days. Wound areas of all rats were measured on days 0 and 14. Tissue samples were taken from the wound areas for histopathologic evaluation of inflammation, epithelialization, and fibrosis. Vascular endothelial growth factor (VEGF), CD4+, and CD8+ expressions were examined by immunohistochemistry. RESULTS: Wound contraction measurements were 63.8%, 80.5%, 88.5%, and 86.6% in the control, LRg, SRg and CRg groups, respectively. Although significant differences were observed for all treated groups (LRg, SRg, and CRg) compared with the control group in terms of wound contraction, there was no difference among the treatment groups. VEGF-positive vessel/mm2 was observed 4.00 ± 0.75, 5.93 ± 0.70, 5.93 ± 1.93, and 7.93 ± 0.70 in the control, LRg, SRg and CRg groups, respectively. There was no difference between LRg and SRg in terms of VEGF expression, but there was significant difference for all other groups compared with each other. CONCLUSION: All usage methods of Rg extract increased wound contraction, and differences were observed compared with the control group. However, the authors believe that the combined usage was more effective due to higher VEGF expression levels and lower CD4+:CD8+ ratio.

Expression of extracellular matrix proteins nidogen-1 and legumain in endometrial carcinomas.

PURPOSE: Our purpose was to comparatively investigate the expressions of nidogen-1 (NID1) and legumain (LGMN) in patients with endometrial cancer, endometrial intraepithelial neoplasia, and proliferative endometrium. METHODS: A cross-sectional, single-center study was performed by the obstetrics and gynecology and pathology departments of our institution. The relationships between descriptive data, clinicopathologic information, and immunohistochemical expressions of NID1 and LGMN were investigated. RESULTS: The histological grades of endometrial cancers (n = 124) as classified by FIGO included 1 (41, 21.1%), 2 (48, 24.7%), and 3 (35, 18.0%). The medians and ranges of deep and superficial NID1 expressions were 50.00 (0-285) and 5.00 (0-100), respectively. The intensity of legumain expression was noted as negative (30, 24.2%), mild (16, 12.9%), moderate (27, 21.8%), or strong (51, 41.1%). Median disease-free survival and overall survival were 75.00 (range: 1 to 170) months and 77.00 (range: 1 to 170) months, respectively. Patients with more intense expression of NID1 and LGMN displayed a higher histological grade. These patients were more likely to have a positive peritoneal cytology, larger tumor size, higher tendency for myometrial or lymphovascular invasion, involvement of ovaries, cervix, omentum, as well as lymph node metastasis, and recurrence. CONCLUSION: Our data indicated that the expressions of NID1 and LGMN may have important diagnostic implications in endometrial pathologies. Further studies should be performed to understand the significance of NID1 and LGMN in the pathogenesis of endometrial tumors.

The Importance of Superb Microvascular Imaging for the Differentiation of Malignant Breast Lesions from Benign Lesions.

OBJECTIVE: In this prospective study, the diagnostic performance of the new version of superb microvascular imaging (SMI) in differentiating malignant from benign lesions was evaluated. MATERIAL AND METHODS: Ninety breast lesions were included. During color SMI examination, both free-hand region of interest (ROI) and box ROI were used. Vascular index (VI) values were obtained from the lesion using both types of ROI and from normal breast tissue via box ROI. VI values, monochrome SMI grading and histopathological results were compared. The efficacy of color SMI and monochrome SMI was investigated in differentiating between benign and malignant breast lesions. RESULTS: The cut-off value, in the differentiation of benign and malignant lesions with color SMI was 0.50 for box ROI, while it was 0.30 for free-hand ROI. The specificity of VI values obtained with box ROI was higher than that of free-hand ROI when differentiating malignant lesions from benign. Comparison of VI values from a lesion and from normal breast tissue showed that VI values in malignant lesions were significantly higher (p<0.05). The VI values of benign lesions and VI values of normal breast tissue were similar. There was a statistically significant relationship between monochrome SMI grading and the malignancy or benign status of the lesion (p<0.001). CONCLUSION: Drawing the lesion circumference free-hand using a free-shape ROI did not enhance the sensitivity and specificity. Contrary to popular belief, a more easy and practical measurement method may be more suitable for SMI examination. It is hoped that this will be one of the earliest studies to assess the clinical performance of the latest version of SMI.

Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation

Abstract The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Results Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. Conclusion These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

Results of Excision of Unknown Papillary Neoplasms Detected on Core Biopsy.

OBJECTIVE: This study aimed to find out valuable parameters that predict the nature of breast papillary lesions before excision, and we compared our results with those in the literature. MATERIALS AND METHODS: We reviewed the medical records and pathology slides of patients diagnosed with papillary neoplasm after undergoing a core-needle biopsy between 2010 and 2020, who, subsequently, underwent surgical excision in a single tertiary care institution. The core biopsy results and pathology results of excision materials were compared with the radiological, pathological, and demographic findings. RESULTS: A total of 51 patients were included in the study. According to the excision results, the patients were divided into two groups: the atypical group, which included 20 patients (39.3%), and the benign group, which included 31 patients (61.7%). The results of the core biopsy showed that the loss of myoepithelial cell layer was identified in 18 patients in the atypical group, while it was present in all patients in the benign group. Tumor sizes were larger and patient ages were older in the atypical group compared with the benign group. No significant difference was found between atypical and benign groups in terms of breast imaging-reporting and data system (BI-RADS) classification and location (right vs left; central vs peripheral). The upgrade rate was between 0% and 16% in literature, while it was 4% in our study. CONCLUSION: There is no consensus on whether patients diagnosed with papillary neoplasia as a result of core biopsy will undergo excision. According to our results, patients with following criteria should have their lesions excised: those who are advanced in age, those who are diagnosed with a papillary lesion as a result of core biopsies with loss of myoepithelial cell layer, and those who are diagnosed with large-sized lesions without loss of myoepithelial cell layer. Patients diagnosed with small-sized lesions without loss of myoepithelial cell layer and who are young in age are to be followed up without the need for lesion excision. The lesions should be adequately sampled.

Incidental ectopic adrenal cortical tissue: Retrospective analysis of 16 patients.

OBJECTIVE: To evaluate ectopic adrenal cortical tissue (EACT) and identify clinical, pathological and radiological aspects. STUDY DESIGN: Retrospective review of pathology reports in a single tertiary institution between 2010 and 2020 was conducted. Patients diagnosed with EACT were included for analysis. Demographic characteristics, accompanying pathologies and clinicopathological and radiological findings of these patients were analyzed. RESULTS: There was a total of 17 patients in the cohort. Fifteen were boys and 2 were adults (1 male). The mean diameter of the EACT nodule was 0.25 cm (range 0.2-0.5 cm). All EACTs were incidentally diagnosed. Seven EACTs were diagnosed during an inguinal hernia repair, 6 during orchidopexy, 1 during partial orchiectomy, 2 during orchiectomy and 1 during hysterectomy and bilateral salpingoophorectomy due to uterine prolapse. DISCUSSION: EACT is a rare entity that is mostly found incidentally during inguinoscrotal interventions. Radiological discrimination of EACT may not be easy and thus, not detected prior to surgery. Clinical significance of EACT is not very well understood, however it tends to be a benign pathology. Although it is more commonly found in children, adults may present with EACT, as well. CONCLUSION: A tiny yellowish nodule detected in the inguinoscrotal region should be suspected for EACT by pediatric urologists, surgeons, and pathologists.

Focal pyloric hypertrophy in adults: a diagnostic pitfall-a case report and review of the literature.

Adult hypertrophic pyloric stenosis in the form of focal pyloric hypertrophy is an uncommon but a well-established lesion. In most cases, clinical findings suggest malignancy, and despite advances in imaging techniques, preoperative diagnosis is difficult. Herein, an example of focal pyloric hypertrophy is presented with a review of the literature to emphasize the clinicopathological characteristics of this lesion. In a 43-year-old man with abdominal discomfort, endoscopy showed a 1.5 cm nodular lesion near the pylorus that necessitated surgery to exclude malignancy. Pathological examination allowed the diagnosis of focal pyloric hypertrophy. The present case and the review revealed that focal pyloric hypertrophy is a male dominant lesion in middle-aged patients. The clinical diagnosis is problematic, and its initial diagnosis depends on a high clinical suspicion in patients with upper gastrointestinal system complaints irrespective of the duration of the symptoms. It is not known whether it is a separate entity from the diffuse form. Although both are similar in a clinical point of view, etiopathogenetic studies are required to clarify their differences completely. Moreover, the rare occurrence of focal pyloric hypertrophy and the lack of diagnostic clinical findings do not exclude its consideration in the differential diagnosis, especially in patients with gastric outlet obstruction.

Incidental Collision Tumor of Hepatocellular Carcinoma and Neuroendocrine Carcinoma.

The composite tumors of the liver are very rare, including the coexistence of HCC (hepatocellular carcinoma) with NEC (neuroendocrine carcinoma). The rare occurrence of these tumors necessitates more reported cases in order to fully understand their clinical characteristics, behaviors and treatments. Herein is described an incidental collision tumor of HCC-NEC, along with a review of the literature focusing on their clinicopathological findings and prognosis. The tumor presented here was found incidentally in the hepatectomy specimen of a 56-year-old man who had undergone liver transplantation for rapidly progressive liver failure because of alcoholic hepatitis and cirrhosis. Imaging and laboratory examinations did not demonstrate tumor-related findings. During macroscopic examination, two sharply defined and distinctive areas (1.7 cm and 0.6 cm dimension respectively) were detected among the cirrhotic nodules. The characteristic histopathological features and immunohistochemical findings allowed a diagnosis of HCC-NEC to be made. There was no evidence of recurrence and metastasis after 10 months following surgery. The present case and review revealed that these tumors are frequently found in older ages and males. Although serum markers are valuable in the discrimination of malignant tumors, their absence cannot completely rule out composite HCC-NEC. Diagnosis requires a comprehensive histopathological evaluation together with immunohistochemistry. The NEC component might influence the treatment strategy and eventually the outcome of the patient. In conclusion, the rare occurrence of HCC-NEC and the lack of diagnostic clinical signs and symptoms do not exclude their consideration in the differential diagnosis of liver tumors, especially in patients with the chronic liver disease.

A study detection of the ROS1 gene fusion by FISH and ROS1 protein expression by IHC methods in patients with ovarian malignant or borderline serous tumors.

OBJECTIVE: ROS1 is an orphan receptor protein tyrosine kinase which is supposed to undergo genetic rearrangement in carcinogenesis. In the current study, we aimed to investigate the frequency and clinicopathologic features associated with ROS1 gene fusion and ROS1 protein expression in patients with ovarian serous carcinoma or serous borderline tumors. MATERIALS AND METHODS: Tissue samples of 102 patients with high or low grade serous carcinoma and borderline serous tumors were selected randomly from the archives of Department of Gyneco-pathology, and analyzed for ROS1 gene expression. (Fluorescence in situ hybridization (FISH) method was used to assess ROS1 gene rearrangement, while ROS1 protein expression was analyzed using immunohistochemistry. RESULTS: The study consisted of 94 cases of high-grade serous carcinoma (92.1%), 2 cases of low-grade serous carcinoma (%2) and 6 cases of serous borderline tumor (5.9%). ROS1 gene rearrangement analysis revealed that 4 patients (3.9%) were FISH-positive; whereas the immunohistochemical analysis yielded only 1 patient (0.9%) exhibiting faint positive expression of ROS1 protein. Given the low incidences of ROS1 gene rearrangement and protein expression, their relationships with clinicopathologic parameters could not be statistically analyzed. CONCLUSION: Although rare, patients with ovarian serous carcinoma or serous borderline tumor may exhibit ROS1 gene rearrangement and ROS1 protein expression. Further large-scale studies are necessary to explore the clinicopathologic significance of ROS1 gene expression in ovarian serous carcinoma.

A rare case of peripherally located non-bronchial pulmonary mucous gland adenoma.

Pulmonary mucous gland adenomas are rare benign tumors, which need to be differentiated from malign lung masses. The differential diagnosis is of particular importance for those arising from lung parenchyma in atypical locations. In this article, we report a 70-year-old male patient, who had complaints of cough and expectoration for almost two years. Chest computed tomography showed a 1 cm nodule at the left lower lobe of lung. The tumor was totally resected with mini-thoracotomy and wedge resection and sent to the pathology department for a frozen examination. The frozen result was reported as benign. The pathological diagnosis was mucous gland adenoma. The patient had no postoperative complication and made a complete recovery. Pulmonary mucous adenomas may rarely originate from lung parenchyma and be seen in patients with peripherally located lung lesions.