PD-L1 and PD-L2 Expression in Different Tumor Stages and Types of Malignant Salivary Gland Neoplasms: A Single-center Experience.

There is a limited amount of data on the role of programmed cell death ligand (PD-L) -1 and PD-L2 in salivary gland carcinomas. We aimed to evaluate the prognostic value of PD-L1 and PD-L2 expressions, which are closely related to immune mechanisms, with respect to salivary gland tumor types and stages. Data from patients with salivary gland masses surgically removed between 2006 and 2021, diagnosed with a malignant salivary gland neoplasm, were retrospectively analyzed. Immunoreactivity for PD-L1 and PD-L2 was performed on resection materials. The mean age of 90 patients was 52.1±18.8 and 46.7% were male. Overall, 55.6% of patients were diagnosed with adenoid cystic carcinoma (ACC), 23.3% with mucoepidermoid carcinoma (MEC), 16.7% with acinic cell carcinoma (AciCC), 3.3% with ductal carcinoma (DC), and 1 patient with pleomorphic adenoma ex carcinoma (PA-ex-CA). In all, 52% of ACC, 12% of AciCC, 24% of MEC, and 12% of DC cases were at stage IV. The tumor diameter, frequencies of lymphovascular invasion, metastasis, positive surgical margin, recurrence, and mortality rates of patients at stages III and IV were significantly larger than those at stages I and II (P<0.05). The percentages of tumor cell score (TCS) and immune cell score (ICS) for PD-L1 were significantly higher among patients with MEC compared with those with other types of tumors (P=0.0011). However, the percentages of combined score (CS) for PD-L1 and tumor cell score for PD-L2 were comparable among tumor types (P>0.05). No significant difference was found in these scores for PD-L1 between tumor stages (P>0.05), but for PD-L2, all patients at stage I had TCS <1% for PD-L2, while all patients at stages II and III, and 92% of patients at stage IV had TCS ≥1% (P<0.0001). High expression of PD-L1 was mostly observed in MEC cases (P=0.0016), while all patients with AciCC had a low PD-L1 expression level (P=0.0206). The mean tumor diameter, rate of lymphovascular invasion, perineural invasion, metastasis, positive surgical margin, recurrence, type of treatment, mortality, and TILs ratio did not differ significantly according to PD-L1 expression level (P>0.05). The percentage of tumor-infiltrating lymphocytes was comparable among negative and positive PD-L1 scores according to both 1% and 5% threshold values (P>0.05). High PD-L1 expression is rare in AciCC, while PD-L1 expression is high in MEC. Our findings underline the importance of future screening for PD-L1 and PD-L2 before patients undergoing immunotherapies in all salivary gland tumors.

Expression of netrin-1 in uterine serous carcinoma and its association with prognosis.

BACKGROUND/OBJECTIVES: At present, there are few biomarkers used to predict the prognosis of uterine serous carcinoma (USC). Netrin-1 may be a promising biomarker candidate. We investigated netrin-1 expression in USC tissues and healthy endometrial tissues to determine its relevance to disease prognosis. MATERIALS AND METHODS: Netrin-1 expression was examined in the tissues of 48 patients with USC and 30 patients with healthy benign endometrial tissues via immunohistochemistry. RESULTS: None of the healthy tissues were stained with netrin-1. In tumor tissues, the overall positivity rate of netrin-1 was 75%, detected as high expression in 17 patients (35%) and low in 19 (40%). Patients who had tumors with no netrin-1 expression (n = 12) had a median overall survival (OS) of 60.0 months (95% confidence interval [CI], 47-98), whereas patients who had tumors with low to strong netrin-1 expression (n = 33) had a lower median OS of 50 months, but the difference was not statistically significant (95% CI, 58-108; P = 0.531). Disease-free survival (DFS) was not statistically significant between the groups (95% CI, 67.7-115.9; P = 0.566). Patients with a tumor diameter ≥2 cm had higher netrin-1 expression than those with a tumor diameter of 2 cm (P = 0.027). We did not find any difference in overall and DFS when age, tumor stage, histology, tumor diameter, p53 status, lymphovascular space invasion, myometrial invasion, and lymph node metastasis were compared according to netrin-1 expression (P > 0.05). CONCLUSION: Netrin-1 was expressed in USC but not in healthy tissues. Its expression was not associated with OS or DFS.

Prognostic significance of T lymphocyte subgroups (CD4 and CD8) in lung cancer patients after neoadjuvant chemotherapy.

OBJECTIVE: The basis for current and future lung cancer immunotherapy depends on our knowledge of molecular mechanisms of interactions between tumor and immune system cells. Interactions that occur between different intratumoral populations of the same cells are important. In our study, we aimed to evaluate relationship between the clinical and prognostic features and T lymphocyte subgroups of patients with lung tumors after neoadjuvant treatment. METHODS: A total of 72 patients were included in our study, including study group, 39 of whom received neoadjuvant chemotherapy. Clinical/radiological/pathological findings of patients and CD4/CD8 staining rates in peritumoral/intratumoral areas were recorded. RESULTS: Our study revealed significantly lower intratumoral CD4 + T cell density and lower intratumoral CD4/CD8 ratio in primary tumor after neoadjuvant therapy (respectively, 0.012 and 0.016). Considering tumor types, when control-study groups were compared, inflammation was statistically significant only in adenocarcinoma subtype; intratumoral CD4/CD8 ratio was statistically significant only in squamous-cell carcinoma subtype (respectively, p = 0.0008 and p = 0.0139). When CD4 + T lymphocytes and CD8 + T lymphocytes and CD4/CD8 ratio were compared between control and study groups in low-stage patients according to clinical stages, only intratumoral CD4 + T lymphocyte values and intratumoral CD4/CD8 ratio were significant (respectively, p = 0.0291 ve p = 0.0154). CONCLUSION: All cell types of innate and adaptive intratumoral immunity can affect lung cancer tissues simultaneously, and these interactions have a very complex structure. Understanding the tumor microenvironment and the different roles of associated cancer immune cells may lead to the discovery of new targets for immunological therapies and increased survival times in lung cancer.

The prognostic value of expressions of STAT3, PD-L1, and PD-L2 in Ta/T1 urothelial carcinoma before and after BCG treatment.

INTRODUCTION: Nonmuscle invasive bladder cancers (NMIBC) are common tumors diagnosed in older individuals and men (median age: 69 years). Immunotherapy is a treatment option in cases resistant to Bacillus-Calmette-Guerin (BCG) therapy. We aimed to evaluate the prognostic role of programmed-cell-death ligand (PD-L)-1 (PD-L1), PD-L2, and signal transducer and activator of transcription 3 (STAT3) expressions, which are closely related to immune mechanisms, in the response to BCG treatment of NMIBC. METHODS: The data of patients at the Ta and T1 stages of the cancer without muscularis propria invasion, who were treated with intravesical BCG therapy between 2017 and 2022 were retrospectively analyzed. Immunohistochemical staining for PD-L1, PD-L2, and STAT3 was performed on transurethral resection materials. RESULTS: The mean age of 59 patients was 66.5 ±7.7 and 83.9% were male. The percentage of patients with complete response to BCG treatment was 66.1% and that of BCG refractory patients was 33.9%. Demographic and clinical data did not differ significantly according to BCG treatment response (P> 0.05). The proportion of patients with tumor-infiltrating lymphocytes (TILs) ≥20% were 9.7% among those with Ta-stage tumors and 46.4% among those with T1-stage tumors (P = 0.0014). The percentages of tumor cell scoring (TCS), immune cell scoring (ICS), combined scoring (CS), and expression levels of PD-L1, PD-L2, and H-score of STAT3 did not differ significantly according to tumor stage and treatment response (P > 0.05). However, the median ICS and CS for PD-L1 and median H-score for STAT3 were significantly higher among patients in T1 stage compared to those in Ta stage (P = 0.0487, 0.0462, 0.0112, respectively). Among BCG refractory patients, median STAT3 of patients in T1 stage was significantly higher than those at stage Ta (P = 0.0356) and the rate of TILs was ≥20% in only 3 patients in T1 stage (P = 0.031). Among all patients, significant positive correlation was found between TCS for PD-L1 and H-score for STAT3 (P = 0.0302); and between ICS for PD-L1 and TCS for PD-L2 (P = 0.0053) and TILs ratio (P < 0.0001). Among BCG-refractory cases, pretreatment and post-treatment TCS for PD-L2 and H-scores for STAT3 were significantly correlated (P = 0.0361 and 0.0021, respectively). CONCLUSIONS: The success of BCG treatment in NMIBC was not related to PD-L1, PD-L2, and STAT3 expression status, but PD-L1 expression was correlated with both PD-L2 and STAT3 as well as TILs rate, but this correlation was lost after BCG treatment.

Monophasic pericardial synovial sarcoma in a turkish female patient: a very rare case with cyto-histopathological findings.

BACKGROUND: The aim was to present a 35-year-old female patient with diagnosis of monophasic primary pericardial synovial sarcoma (PSS) with cytopathological findings. CASE PRESENTATION: The case with back pain, palpitation and weakness, was diagnosed with pericardial effusion and suspicious mass adjacent to right heart in ultrasonography. Computerized tomography showed mass 12 × 11 × 6.5 cm in size, located in right mid-anterior pericardial area, with heterogeneous internal structure, heterogeneously contrasting right heart and prominent pressure on superior vena cava. Cytopathology of pericardial effusion showed monotonous cells with oval-spindle vesicular nuclei, less amphophilic cytoplasm, evenly distributed chromatin and inconspicuous nucleoli. The pericardial mass was resected incompletely, spindle cell mesenchymal tumor with hypercellular fascicular structure and with infiltrative margins, containing a small amount of loose myxoid stroma, occasionally necrotic areas was observed histopathologically. Immunohistochemical positive reaction was for vimentin, Bcl-2, TLE-1. Accordingly, the case was diagnosed with monophasic PSS. CONCLUSIONS: This case of monophasic primary PSS was an extremely rare malignancy diagnosed with the cytopathological findings.

Pulmonary placental transmogrification: a difficult pattern in differential diagnosis of pulmonary hamartomas from a tertiary care hospital in Turkey.

OBJECTIVE: Pulmonary placental transmogrification (PT) is a benign lesion curable by resection, represented by an unusual peculiar morphological variation including placentoid bullous change in the pulmonary hamartoma. In this retrospective study, we aimed to examine the histopathological features of pulmonary hamartomas in lung, to evaluate the different histological components, especially PT, and to investigate importance of PT pattern and its relationship with other clinicopathological features. METHODS: Thirty-five cases of pulmonary hamartomas were recruited from the records between 2001 and 2021, divided into two groups according to presence of PT, as PT (-) and PT (+) in pathological examination. RESULTS: 77.1% of all patients were male. There was no significant difference between the two groups in terms of age, sex, comorbidity, presence of symptoms, tumor localization, and radiological findings (P > 0.05). Pulmonary hamartomas were resected totally from 28 patients (80%). Five of these patients (17.9%) had PT components in resection materials with varying degree between 5 and 80%, and all were from male patients. Examination with frozen sections were performed in 15 PT (-) and 5 PT (+) patients but diagnosis with frozen sections was not achieved in any of PT (+) patients. Most of materials included chondroid components (52.22 ± 29.7%) in both groups (P < 0.05). CONCLUSION: The placental papillary projections are available patterns associated with a pulmonary hamartoma and these projections observed especially in frozen sections are very crucial to recognize PT pattern in hamartomas, as they can result in confusions in differential diagnosis of malignities.

Multiple primary intraosseous meningioma mimicking fibrous dysplasia: a case report.

Primary intraosseous meningioma (PIM) is a rare subtype of primary extradural meningiomas. These rare ectopic meningiomas have been usually reported in the frontotemporal regions of the calvarium, orbits, and anterior cranial fossa. We report a case with bilateral tumors located in frontoparietal regions of calvarium. Our initial diagnosis was fibrous dysplasia but the lesions were seen to expand under follow-up. One was resected and the histopathological diagnosis was PIM. This is the second reported case of multiple PIM.

Effects of different scar types on flap viability in a skin flap model: an experimental study.

BACKGROUND: The purpose of this study was to investigate the use of tissues with multiple traumas, scarred pedicles, and medial scarring as a flap. METHODS: Forty-eight rats were randomly divided into four equal groups. The modified McFarlane flap was chosen as the flap model. In Group 1 (control), a dorsal skin flap was elevated and then sutured back into original position. In the other groups, a two-phase procedure was used. In Group 2 (pedicle incision), scar tissue was created with a skin incision at the prospective pedicle site of the flap and then sutured to its original site. In Group 3 (preconditioning), multiple full-thickness traumas were performed along the entire flap body, and in Group 4 (middle incision) scar tissue was created with a skin incision at the prospective middle region of the flap. Then, after 45 days, dorsal flaps were raised in all rats and then sutured back into position. Seven days later, flap survival was evaluated through microangiography and histological evaluation of flap segments. Histopathological examination included assessment of the number of vessels, necrosis, infiltration with polymorphonuclear leukocytes, edema, fibrosis, inflammation, increase in fibroblast activity, and neovascularization. RESULTS: The flap survival rates were 66.78% in Group 1, 68.05% in Group 2, 68.5% in Group 3, and 60.01% in Group 4. The flap survival rate was significantly lower in Group 4 (p < 0.05). There was no significant difference in flap survival between Groups 1, 2, and 3. On microangiographic examination, the vascular network extended more distally and was densest around the scar line in Group 2. Vascularization was poorest in Group 4. On histological examination, the number of vessels tended to be greatest in Groups 3 and 4 but this was not significantly different between groups (p < 0.05). DISCUSSION: The study findings showed that it may be possible to raise a flap from a previously mutilated site secondary to scar formation and multiple full-thickness traumas along the flap body. However, distal necrosis may occur in situations when the scar is positioned in the middle region of the prospective flap.

Protective effects of rectal ozone administration on colon anastomoses following radiotherapy.

BACKGROUND: Anastomotic leakage (AL) following rectal surgery is associated with increased mortality and morbidity. Neoadjuvant radiotherapy disrupts the wound healing process in rectal surgery. OBJECTIVES: To evaluate the effects of intra-rectal ozone application on rectal anastomoses after radiotherapy. MATERIAL AND METHODS: This study was performed on animals. Thirty-two male Wistar rats were randomly divided into 4 groups: control group, ozone group, radiotherapy group, and radiotherapy/ozone group. Ozone was administered intrarectally in the ozone group and water was administered intrarectally in rthe control group for 5 days. The radiotherapy group received 20 Gy of pelvic radiotherapy. The radiotherapy/ozone group received 20 Gy of pelvic radiotherapy after the administration of ozone. Afterward, colon resection followed by an anastomosis were performed under general anesthesia in all groups. Anastomotic segments were resected to evaluate tissue hydroxyproline (HYP) and myeloperoxidase (MPO) levels, perform a histological evaluation, and measure bursting pressure. RESULTS: There were no statistically significant differences between groups regarding tissue MPO levels (p = 0.55). Tissue HYP levels were significantly decreased in the radiotherapy group (p = 0.04). Bursting pressure was found to be significantly lower in the radiotherapy group (p < 0.05). No significant differences were found between adhesion scores in the control and ozone groups. Exudate formation was significantly lower in the radiotherapy group (p < 0.05). The lowest macrophage scores were found in the radiotherapy group (p < 0.05). Fibroblast scores were the highest in the control group and the lowest in the radiotherapy group (p < 0.05). CONCLUSIONS: Intra-rectal ozone application significantly improved the anastomotic healing process after radiation exposure.

Serum cholecystokinin levels can be a predictive factor for difficult cholecystectomy: Decreased cholecystokinin receptor levels.

BACKGROUND: Laparoscopic cholecystectomy (LC) is being performed frequently in general surgery practice. Estimation of difficult cholecystectomy is very important to take precautions against complications. Cholecystokinin (CCK) is an important enzyme for gall-bladder motility. CCK receptor is the target for CCK. Fibrosis and emptying problems of gallbladder are related with difficult cholecys-tectomies. We aimed to evaluate the association between plasma CCK and difficult cholecystectomy and try to explain the mechanism. METHODS: Prospective cross-sectional study was conducted on a group of patients with cholelithiasis Patients who underwent elective cholecystectomy were classified into easy, difficult and very difficult preoperatively using LC difficulty scores. Pre-operative gallbladder empting ratios were measured by ultrasonography. Serum C-reactive protein, and postprandial serum CCK and pancreas polypeptide levels were measured before the operation. Operation data including operation times, adhesion scores, and complications were collected. Tissue CCK receptor levels and tissue fibrosis scores were obtained. RESULTS: Easy, difficult, and very difficult LC (DLC) groups were consisted of 34, 28, and 8 patients, respectively. Gallbladder emp-tying was 60% in easy LC group, but 15% in very DLC group. Plasma CCK levels in easy group (37.4 pg/ml) were significantly lower than plasma CCK levels of difficult (58.6 pg/ml), and very difficult groups (66.23 pg/ml). Tissue CCK receptor levels of easy, difficult, and very difficult were 372.4, 178.3, and 144.1 ng/100 mg, respectively. Adhesion scores and fibrosis scores of very difficult group were significantly higher than other groups. Operation times were significantly longer in very difficult group. There were two conversions to open in very DLC group (25%). CONCLUSION: CCK is a reliable parameter for determining the difficulty of LC. Decreased CCK receptor levels with fibrosis of gallbladder are the probably responsible mechanism.

Radiological, Clinical, and Histological Findings in the Treatment of Pilonidal Sinus with Phenol Injection.

Objective: Sacrococcygeal pilonidal disease is a chronic discharging wound that causes pain and loss of quality of life. Phenol application is an outpatient procedure with low complications and low recurrence rates. We evaluated the radiological, histological, and clinical results of phenol application. Methods: A total of 44 consecutive patients with sacrococcygeal pilonidal disease underwent phenol application in Kocaeli University Faculty of Medicine, General Surgery Clinic between December 2015 and March 2017. Demographics, complaints, symptom duration, and the number of sinuses were recorded. Patients were examined using ultrasonography (USG) before surgery and two months after surgery. Four patients who wanted rhomboid excision and Limberg flap procedure underwent preoperative local phenol application and were excluded from the study. The excised tissues were used for pathological evaluation. Results: Purulent discharge was the leading symptom. All of the patients had hair in the preoperative USG evaluation, whereas five patients had still hairs in the sinuses in the postoperative USG examination. Four of these cases had recurrences on a 2-month follow-up. After phenol application, a 10% volume decrease was observed. Pathological examination was performed in four cases with phenol application, and in pathological material, the sinuses looked sclerotic and fibrotic. Conclusions: Our study revealed that a single phenol application achieved 90% success. However, no significant difference was observed in the cavity volume after phenol injection.

The Value of Immunohistochemical Methods and Preoperative Magnetic Resonance Imaging Findings in Diagnosis of IDH1 Mutant Glioblastomas.

AIM: To assess the presence of isocitrate dehydrogenase (IDH) 1 mutation in glioblastomas using real-time polymerase chain reaction (RT-PCR), which is the gold standard in the diagnosis of IDH1 mutation; by immunohistochemistry (IHC), which is available in most of the pathology laboratories; and by preoperative magnetic resonance imaging, which is a non-invasive method. We also investigated the relationship between these methods and their usability in routine practice. MATERIAL AND METHODS: RT-PCR was performed to evaluate the presence of IDH1-R132H mutation on the blocks of 70 patients diagnosed with glioblastoma, and IDH1 stain was applied to the same blocks as IHC. Radiologically, preoperative magnetic resonance images of the patients were reviewed in terms of tumor size, localization, and presence of non-contrast-enhancing solid tumor component. RESULTS: Evaluation by RT-PCR revealed that 15 (21.4%) patients were IDH-mutant, whereas IHC examination revealed 13 (18.6%) and radiological evaluation revealed 11 (15.7%) patients were IDH-mutant. There was a statistically significant difference between the IDH1 mutation detected by RT-PCR and by IHC or radiological methods (p=0.034 and p=0.000, respectively). The sensitivity and specificity of IHC method in detecting IDH1 mutation were 86.6% and 100%, respectively, whereas those of radiological methods were 33.3% and 89%, respectively. CONCLUSION: Conclusively, radiological and IHC methods can be used in cases where RT-PCR cannot be applied for detecting IDH1 mutation. However, the results need to be confirmed by RT-PCR when necessary as these methods may sometimes overlook some IDH-mutant patients.

Giant exophytic tumor of the leg: A case report of amyloidoma with literature review.

Amyloidosis is a heterogeneous group of diseases with the most common form being systemic distribution. The least common type of the disease is tumor formation due to deposition which is called "amyloid tumor (amyloidoma)". Although such tumors can occur in any region of the body, extremity localization is fairly seldom. Here, we report the clinical and histopathological features of amyloidoma in an 81-year-old female patient who presented with a large rapidly growing mass in the left lower extremity.

An Incidental Chorda Tympani Schwannoma Identified During Middle Ear Surgery.

Chorda tympani schwannomas are rare benign tumors of the middle ear cleft. This is a case of incidental chorda tympani schwannoma identified intraoperatively. The patient was a 50-year-old male with chronic active otitis media complicated by left-sided facial paralysis. During closed mastoidectomy and tympanoplasty approach, a well-demarcated swelling on the left chorda tympani nerve was identified and sectioned for pathologic evaluation. The histopathologic evaluation established the diagnosis of schwannoma. Although the tumor was unlikely the cause of the disease process in this patient, his facial paralysis and middle ear disease were resolved after surgery.

A single-center experience with giant cell tumors of sphenoid bone and clivus.

OBJECTIVE: To present pathologic, clinical, and treatment findings for giant cell tumors (GCTs) of sphenoid bone and clivus. METHODS: We describe the optimal treatment algorithm in patients with a histopathologic diagnosis of bone GCT by presenting the effects of denosumab treatment in both pediatric and adult patients with GCT undergoing endoscopic transnasal surgery. Clinicopathologic correlation is crucial for the differential diagnosis of GCT and the choice of treatment modality. CONCLUSION: GCT of bone is a local aggressive tumor that accounts for about 3%-7% of all bone tumors. GCTs located in the cranium are extremely uncommon neoplasms. There are no defined guidelines for the treatment of GCTs in skull base. Following surgical resection of the tumor, the addition of denosumab treatments to radiotherapy has a significant role in preventing the recurrence of GCT and in promoting regression of residual tumor size.

Breast Recurrence of Acute Myeloid Leukemia After Bone Marrow Transplantation: A Case Report About Myeloid Sarcoma of the Breast.

Myeloid sarcoma of the breast is a rare malignancy, can be seen after bone marrow transplantation. Although there are no specific features for this malignancy which is difficult to diagnose, some common features draw attention in the published case reports. Since there is no consensus on the treatment of myeloid sarcoma of the breast, we aimed to explain our own diagnosis and treatment methods in this case report.

Infiltration of thyroid papillary cancer tissue with myeloid leukemic cells: a case report.

BACKGROUND: Extramedullary leukemia, also known as myeloid sarcoma, is a rare form of acute myeloid leukemia and often accompanies bone marrow involvement. Myeloid infiltration of the thyroid gland is extremely rare. Here, a unique case in which thyroid cancer tissue was infiltrated with myeloid cells is presented. CASE PRESENTATION: We present a case of thyroid papillary cancer infiltrated by blastic cells and bilateral breast and axillary myeloid sarcoma in a 30-year-old Caucasian female patient with a history of osteosarcoma and MDS-RAEB2. The patient firstly received 6 cycles of chemotherapy for osteosarcoma, and allogeneic hematopoietic stem cell transplantation was performed after anthracycline-based chemotherapy due to MDS-RAEB2. The patient remained in remission on follow-up in terms of both osteosarcoma and MDS-RAEB2. Malignant features (Bethesda VI) were observed in the fine needle aspiration biopsy performed from a newly developed firm, fixed thyroid nodule approximately 4-5 cm in length in the left thyroid lobe. Because of the Bethesda VI thyroid nodule, the patient underwent total thyroidectomy. In the pathological evaluation, CD34-, CD117-, MPO-, and HLA-DR-positive blastic cells which infiltrated into follicular variant papillary thyroid carcinoma were detected. In the evaluation performed due to blastic cell infiltration, multiple lesions showing increased 18-fluorodeoxyglucose activity in bilateral breast and axillae were detected. Myeloid sarcoma was found as a result of tru-cut biopsy from these lesions. A fungal cystic lesion was detected in the frontal region of the patient who developed altered consciousness after the second cycle of treatment of myeloid sarcoma. During her follow-up in the intensive care unit, she died of cranial septic embolism and acute infarction. CONCLUSIONS: Here, we present a very interesting case that is the first. A staged approach to diagnosis with methods including immunohistochemical staining, radiological imaging methods, and cytogenetic and molecular analyses can help make the definitive diagnosis.