Bilateral metaplastic squamous cell breast cancer.

ABSTRACT: Metaplastic breast cancer is a rare and heterogeneous breast cancer group that encompasses both malign epithelial and mesenchymal tissue components. Squamous cell breast cancer (SCC) is one of the types of metaplastic breast cancer, and diagnosis is established when more than 90% of the malignant cells are of squamous cell origin. Squamous cell metaplastic breast carcinoma is considered an aggressive tumor because of the risk of distant metastases, and there are limited data on treatment patterns. In this study, we report patient characteristics and treatment results of one patient with bilateral metaplastic squamous cell breast cancer.

Differential cyclin-E1 expression in CIC-rearranged sarcoma.

CIC-rearranged sarcoma (CRS) is a group of high-grade undifferentiated small round cell sarcomas examined as a separate entity in the current WHO classification; since it shows more aggressive clinical behavior and distinct morphological and molecular features compared to Ewing sarcoma (ES). As CCNE1 expression is associated with tumor growth in CIC::DUX4 sarcomas, we aimed to demonstrate the value of cyclin E1 expression in CRS. Cyclin E1 immunohistochemistry and break-apart FISH for EWSR1 and CIC gene rearrangements were performed on 3-mm tissue microarrays composed of 40 small round cell tumors. Five cases were classified as CRS, whereas 22 were ES and 13 were unclassified (EWSR1-/CIC-). Among all three diagnostic groups, we found cyclin E1 expression level to be higher in CRS (80 %) and unclassified groups (61.5 %) compared to ES (4.5 %, p < 0.001). In addition, high cyclin E1 expression levels were associated with higher mean age at diagnosis, presence of atypical histology and myxoid stroma, low CD99 expression, and presence of metastasis at diagnosis. The sensitivity and specificity of high cyclin E1 expression in detecting non-ES cases were 95.5 % and 66.7 %, respectively. However, the correlation between cyclin E1 expression level and survival was not statistically significant. This is the first study that shows cyclin E1 immunohistochemical expression in EWSR1-negative undifferentiated small cell sarcomas, particularly CRS.

Does the Distance of the Tumor from the Surgical Margin Affect Biochemical Recurrence in Patients with Pathological Organ-Confined Prostate Cancer?

OBJECTIVE: To investigate the effect of the distance between tumor and surgical margin on biochemical recurrence in patients with organ-confined prostate cancer. MATERIAL AND METHOD: The data of 208 patients, who underwent radical prostatectomy between 2012-2018, were retrospectively analyzed. The surgical margin status of 147 pathologically organ-confined patients was categorized as positive, close ( < 1mm) and negative. Surgical margin status and parameters affecting biochemical recurrence were examined. Furthermore, multivariate analysis was done to determine the parameters associated with biochemical recurrence. RESULTS: Biochemical recurrence was detected in 21 (14.2%) of 147 patients. 38 (27.9%) men had negative surgical margins, 68 (46.2%) had close surgical margins and 41 (25.9%) had positive surgical margins. Tumor volume and ISUP grade were found to be statistically significant for positive surgical margin and close surgical margin patients compared to negative surgical margin patients. Close surgical margin was not statistically associated with biochemical recurrence. Preoperative high PSA (p < 0.001) and positive surgical margin (p=0.021) were independent risk factors for biochemical recurrence. CONCLUSION: According to our results, it is not necessary to include the presence of a close surgical margin in the pathology reports in patients with pathological organ-confined tumors and negative surgical margins.

The Relationship of Mutation Carriage of BRCA1/2 and Family History in Triple-Negative Breast Cancer: Experience from a Diagnostic Center in Turkey.

OBJECTIVE: BRCA1/2 genes play a role in the etiopathogenesis of 10%-30% of triple-negative breast cancer (TNBC). This study aims to investigate the BRCA1/2 genes and the demographic and clinicopathological features in patients with TNBC. The study also examined the impact of cancer history of TNBC individuals' relatives on the risk of BRCA1/2 mutation carriership rate. MATERIALS AND METHODS: The BRCA1/2 genes of 65 women diagnosed with TNBC between 2011 and 2017 were investigated using next-generation sequencing. We analyzed the correlations of patients' demographic and clinicopathologic parameters and family history with BRCA1/2 mutation status. We used the χ2-test, t-test, Mann-Whitney U test, and logistic regression statistical methods. RESULTS: The BRCA1/2 mutation carrier rate was 16.9%. Patients who had BRCA1/2 mutations were compared with those who did not in terms of demographic and clinicopathological parameters. In the BRCA1/2 mutation carrier group, the Ki-67 index and the number of relatives with cancer were higher than the BRCA1/2 non-carrier group. Logistic regression analysis revealed that when the number of relatives with breast or ovarian cancer was ≥2, the risk of carrying the BRCA1/2 mutation increased by 15-fold. Regardless of the type of cancer (including cancers in other organs besides breast or ovary), the risk of carrying the BRCA1/2 mutation increased 1.3 times with each increase in the number of relatives with cancer for the patient with TNBC. CONCLUSION: In cases with a diagnosis of TNBC, a significant relationship exists between the number of relatives with cancer in the family history and the risk of carrying mutations in the BRCA1/2 genes. This relationship can be confirmed further by large-scale studies with more cases.

PD-L1 expression in immune cells is a favorable prognostic factor for nasopharyngeal carcinoma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) has been determined as a reliable prognostic factor for various malignancies. In this study, we aimed to determine the prognostic effect of PD-L1 expression in tumor-infiltrating immune cells (TIICs) of nasopharyngeal carcinoma (NPC) patients. METHODS: Seventy patients diagnosed with non-metastatic NPC were included in the study. PD-L1 expression on immune cells was analyzed by immunohistochemical method. Patients were categorized into two groups according to the PD-L1 expression level in TIICs (level of PD-L1 staining ≥5% positive vs <5% negative). RESULTS: Median follow-up period was 34 months (range = 1 - 188). 1 and 2 years survival rate were found as 75% and 63% in PD-L1 negative TIICs group (47%), and 85% and 83% in PD-L1 positive TIICs group (53%), respectively. PD-L1 positivity in immune cells (ICs) was detected in 53% of the patients. The survival rate was found better in the PD- L1 positive group compared to the negative group (P = 0.049). DISCUSSION: In conclusion, the survival rate was found significantly better in the PD-L1 positive TIICs group, compared to the negative group.

Good prognostic factor in patients with nonmetastatic nasopharyngeal carcinoma: Programmed death ligand-1 expression in tumor cells.

PURPOSE: Programmed death ligand-1 (PD-L1) is the main ligand for programmed death-1 (PD-1), and is one of the major targets for cancer immunotherapy. Only a few studies are available for the clinical significance of PD-1/PD-L1 in nasopharyngeal carcinoma (NPC). There is a controversial association between PD-L1 expression and survival in NPC. This study aimed at defining any potential association between PD-L1 expression in tumor cells (TCs) and prognosis in NPC. PATIENTS AND METHODS: A total of seventy NPC patients treated between January 2008 and December 2016 were included in the study. PD-L1 expression was assessed by immunohistochemistry (IHC) in tumor specimens. The IHC assay was considered positive if ≥5% of TCs are stained. Clinicopathological variables were documented. Variables included in the analysis were PD-L1 expression, clinicopathological characteristics, and prognosis. RESULTS: The estimated 5-year overall survival (OS) rate was 62%. Nearly 55.7% (n = 39) of the TCs tested positive for PD-L1 expression. No associations were found between the level of PD-L1 in TCs and clinicopathological characteristics. Comparisons between patients with PD-L1-positive tumors and PD-L1-negative tumors revealed that OS was statistically significantly longer in patients with PD-L1-positive tumors as assessed by the univariate Cox regression analysis (hazard ratio [HR], 0.378; 95% confidence interval, 0.158-0.905; P = 0.029) and Kaplan-Meier curves (P = 0.023). CONCLUSION: PD-L1 expression is an important prognostic factor in NPC. PD-L1 expression positively correlates with survival.

A case of pelvic giant cell tumor of bone, complete remission with denosumab: long duration of response.

Although giant cell tumor of bone has been considered as a disease with benign course, it can lead to bone destruction and serious morbidity. A 19-year-old case was presented with hip pain. There was a recurrence after 9 months of curative surgical resection and zoledronic acid use, and as surgical morbidity would be high, antiosteoclastic receptor activator of nuclear factor kappa B ligand inhibitor denosumab treatment was administered. She had a complete remission after 18 months of denosumab treatment. The important point in the present case is that it has been followed up without recurrence after around 42 months of denosumab use and 11 months of follow-up after the cessation of drug. In recurrent cases in which nonmetastatic surgery is not suitable, the use of denosumab decreases tumor progression. The duration of use in unresectable and advanced cases still remains unclear.

Novel BRCA2 pathogenic genotype and breast cancer phenotype discordance in monozygotic triplets.

BRCA1/2 genes with high-penetrance are tumor suppressor and tumor susceptibility genes that play important roles in the homologous recombination mechanism in DNA repair and increase breast cancer risk. Variants in BRCA1 or BRCA2 are the main causes of familial and early-onset breast cancer. This study investigated pathogenic variant belonging to the BRCA2 gene splice region in monozygotic triplets. A 44-year-old woman was diagnosed with breast cancer when she was 32 years old. Her monozygotic sister had a history of breast cancer. No malignancy was detected in the third one of the monozygotic triplets. Sanger sequencing was used to evaluate the BRCA1/2 gene status of the patient and family members. It was figured out that they had the same genetic variant, a heterozygous germ-line splice region variant (c.7008-1G > C) in the BRCA2 gene. This novel splice region variant may be a new pathogenic variant of the BRCA2 gene. Its association with breast cancers needs to be further verified in more patient cases.

Location and Frequency of Residual Breast Tissue after Mastectomy.

INTRODUCTION: Residual breast tissue after mastectomy is a problem since breast cancer can arise from it. The aim of this study was to investigate the incidence and location of residual breast tissue following modified radical mastectomy. METHODS: 111 consecutive breast cancer patients who underwent mastectomy were enrolled in this study. During surgery, after removal of the breast tissue and before skin closure, a 1-cm2 tissue sample was obtained from each quadrant under the skin flaps. These samples were evaluated histopathologically for the presence of any residual breast tissue. RESULTS: Residual breast tissue was detected in the tissue samples of 12/111 (10.8%) patients. 4 of these patients had residual breast tissue in all 4 quadrants. 6 patients had residual tissue in a single quadrant. With 9 positive biopsy results, the upper medial quadrant was the most frequently involved location. The other quadrants had 6 positive biopsy results each. At the end of a median of 20 months of follow-up, none of these patients developed breast cancer recurrences. CONCLUSION: Mastectomy has a high probability of residual breast tissue being left behind. Physicians should be aware of this and act accordingly when planning surgical or follow-up treatment.

Blood Vessel Invasion in Endometrial Cancer Is One of the Mechanisms of Spread to the Cervix.

To evaluate the association between type of invaded vessels (blood or lymphatic) and cervical involvement in endometrial cancer (EC). Pathological slides of 93 patients with EC who had vascular space invasion in hematoxylin-eosin staining underwent immunohistochemical assay with CD31 and podoplanin. CD31 and podoplanin were used to identify blood and lymphatic invaded vessels, respectively. Cervical stromal invasion (CSI) was determined in 21 (30%) patients. The rate of CD31-positivity was significantly higher in patients with CSI than without (76.2 and 34.7%, p = 0.001; respectively). Podoplanin-positivity was determined in 47.6 and 81.6% of patients with and without CSI, respectively (p = 0.005). Age, myometrial invasion and the combination of CD31-positivity with podoplanin-negativity were found as independent predictors for CSI. Blood vessel invasion is an important factor for CSI in EC. Blood vessel invasion rather than lymphatic vessel invasion is one of the predominant ways by which EC spreads to the cervix.

A rare localization of an extrapleural solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare neoplasm that generally originates in the pleura. Extrapleural locations are rare. In such cases, a definitive preoperative diagnosis is often difficult, because neither radiological nor cytological examinations are exhaustive. Therefore, surgical excision is frequently the only way to reach the correct diagnosis and to provide definitive treatment. The case is here described of a solitary fibrous tumor of the soft tissue in the subscapular area in a 50-year-old male.

Is testis-sparing surgery safe in small testicular masses? Results of a multicentre study.

INTRODUCTION: Our goal was to evaluate benign and malignant lesions and testicular intraepithelial neoplasia (TIN) in the neighbouring normal-appearing testis tissue in men who underwent radical orchiectomy for testicular mass with a pathologic tumour size of ≤3cm. METHODS: In this retrospective, multicentre study, data of 252 patients from 11 different institutions were included. Patients were divided into three groups based on tumour size: Group 1 (0-1 cm; n=35), Group 2 (1.1-2cm; n=99), and Group 3 (2.1-3 cm; n=118). Benign lesions and TIN were sought in the neighbouring testicular tissue and compared between groups. RESULTS: Mean patient age was 32.3 years. Benign lesions were reported in 54.3%, 33.3%, and 14.4% of Groups 1, 2, and 3, respectively (p<0.05 between groups). TIN was detected in 20%, 42.4%, and 41.5% of Groups 1, 2, and 3, respectively (p<0.05 for Group 1 vs. Groups 2 and 3; p>0.05 for Groups 2 vs. 3). Multifocality was detected in 8.6%, 4%, and 0% of Groups 1, 2, and 3, respectively (p<0.05 for both Group 1 vs. Group 3 and for Group 2 vs. Group 3; p>0.05 for Group 1 vs. Group 2). A tumour cutoff size of 1.5 cm was found to be significant for detecting benign tumour. TIN and multifocality rates were similar in patients with a tumour size of ≤1.5 vs. >1.5 cm (p>0.05). CONCLUSIONS: Benign lesions and TIN in the neighbouring testis were significantly decreased and multifocality was increased in patients with a tumour mass size of ≤1 cm. Testis-sparing surgery should be performed with caution and a safety rim of normal tissue should also be excised.

Giant retroperitoneal dedifferentiated liposarcoma.

INTRODUCTION: Liposarcoma is the most frequent type of retroperitoneal sarcomas. Dedifferentiated liposarcoma is the least common subtype and is an extremely rare tumor. CASE REPORT: We present the case of a 53-year-old male who was referred with a giant retroperitoneal mass. The patients' mass was deemed unresectable by the previous institution and received chemotherapy with no benefit. We macroscopically removed the 38x32 cm mass with right nefrectomy. Pathological examination revealed dedifferentiated liposarcoma. CONCLUSION: Surgery is the gold standart in the treatment of retroperitoneal sarcomas. Giant masses present a challenge for the surgeon with possible major vascular injuries and multiorgan resections. Therefore it is important for these patients to be referred for surgery without delay. KEY WORDS: Dedifferentiated liposarcoma, Liposarcoma, Retroperitoneal sarcoma.

VEGF receptor subtypes may serve as novel prognostic factors and putative indicators for anti VEGF receptor treatment response in renal cell carcinoma cases.

PURPOSE: Targeted therapies are novel treatment options for renal cell carcinoma (RCC). Of the target molecules investigated, vascular endothelial growth factor receptors (VEFGRs) were seldom evaluated. The current study investigated the prognostic significance of VEGFRs and IMP-3 as a potential prognostic markers. METHODS: Pathological material and clinical files of 100 patients with RCC were retrospectively evaluated. For each case, the clinical outcome and disease stage were assessed and resected materials were histologically reevaluated. VEGFR-2, VEGFR-3 and IMP-3 expression of tumor samples were analyzed with immunohistochemistry. These expressions were compared with prognosis and clinicopathological variables. RESULTS: Five-year overall survival (OS) was 80% in the whole cohort. Mean survival was 20.3±1.9 months in metastatic disease (95%CI:16.4-24.2). Two-year OS was 20% and 5-year OS was zero in the metastatic group. Survival was significantly longer in VEGFR-2 expressing group than in the nonexpressing group (78.7±2.6 vs 63.9±6; 95%CI:73.7-84 and 52.1-75.7, respectively; p=0.031). VEGFR-3 and IMP-3 expressions were not significantly correlated with survival. In the non-metastatic group mean OS was 82.6±2.1 months and 2- and 5-year OS were 96 and 88%, respectively. CONCLUSIONS: Since VEGFRs were expressed on all histological subtypes and significantly correlated with survival, assessment of VEGFR-2 and VEGFR-3 on tumor samples might serve as a putative prognostic factor in RCC cases. These expressions might identify a subset of patients that may benefit from antiangiogenic treatments targeting VEGFR receptors.

p16 expression predicts neoadjuvant tumor necrosis in osteosarcomas: reappraisal with a larger series using whole sections.

The presence of greater than or equal to 90% necrosis after neoadjuvant chemotherapy is a favorable prognostic factor in osteosarcomas. A recent study using tissue microarrays of 40 conventional osteosarcomas showed that p16 expression independently predicted the necrotic response to neoadjuvant chemotherapy. In this study, we investigated this finding using whole sections in a larger group of osteosarcomas. Cases of 83 patients who had pretreatment biopsies and received neoadjuvant chemotherapy and surgical resection were collected from 3 reference hospital archives. Age, sex, tumor size, tumor subtype, location, and percentage of tumor necrosis were recorded; 4-µm sections from pretreatment biopsies were stained for p16. More than 30% strong nuclear staining was regarded as positive. The median age was 17 years (5-68 years), and male/female ratio was 2.3. The mean tumor diameter was 9.9 cm (2-30 cm). Tumors were most commonly of the osteoblastic type (60%) and located at the femur (47%). p16 positivity was seen in 66% of the patients. The median pathologic necrosis was 65%, and 39% of the patients responded favorably (≥%90 necrosis) to neoadjuvant therapy. In univariate analysis, p16 expression significantly correlated with greater than or equal to 90% response (P = .022). On multivariate analysis, p16 expression (odds ratio [OR], 7.71; P = .008), female sex (OR, 8.62; P = .006), and smaller tumor size (OR, 0.86; P = .023) were independent predictors of favorable response to neoadjuvant chemotherapy. We confirmed the finding that p16 expression predicts postchemotherapy necrotic response in conventional osteosarcomas.

Can Burkitt's Lymphoma and Hodgkin's Lymphoma occur in siblings simultaneously?

Familial clustering of Hodgkin lymphoma (HL) and increased risk of developing disease among the siblings has been reported earlier. Usually familial lymphoma in sibling pairs occurs in the pairs of either non-Hodgkin lymphoma or HL. In the familial HL, same type of human leukocyte antigens (HLA) is responsible in the affected family members. There are also some studies stating "Killer cell immunoglobulin like receptor (KIR)" genotypes can be important in the etiology of familial HL. Here we report two siblings; one with Non-Hodgkin and the other with Hodgkin lymphoma which showed Epstein-Barr virus encoded small RNAs positivity in the tumor tissues. We have also found that their HLA genotypes are same with each other. In addition, we have discussed familial lymphoma pathogenesis and HLA haplotypes.

Chondroblastoma of the medial cuneiform bone in a 32-year-old woman.

UNLABELLED: Patient: Female, 32. FINAL DIAGNOSIS: Chondroblastoma. SYMPTOMS: Pain. MEDICATION: -. CLINICAL PROCEDURE: -. SPECIALTY: Oncology. OBJECTIVE: Unusual clinical course. BACKGROUND: 1% of all bone tumors are Chondroblastomas. Chondroblastomas, initially considered to be an osteoclastoma variant are benign, cartilaginous tumors which usually occur in the epiphysis of long bones, especially in the humerus, tibia, and femur, most common in children and young adults between the ages of 10 and 20 years. 4% of all chondroblastomas settle in the talus whereas cuneiform and other tarsal bones are very rare sites for the development of this benign chondroid lesion. CASE REPORT: A case of chondroblastoma involving the medial cuneiform of the left foot of a 32 year old woman is described. The patient presented with moderate localized pain and tenderness over the medial aspect of her left foot. Radiographs showed a lytic expansile lesion within the right cuneiform bone indicating a bone tumor. Biopsy demonstrated cellular areas made up of round, polygonal cells, with round-oval nucleus and chondroblasts that appear with a thin calcification rim. Intralesional curettage and synthetic bone grafting with PRP (Platelet-Rich Plasma) application was performed for its treatment. After 18 month follow up, osteointegration was observed with the defect completely filled and the patient was free of disease and pain. CONCLUSIONS: A painful, expansile, thin, sclerotic lesion detected at the cuneiform should arise suspicion for chondroblastoma even at age over 20 years. Meticulous curettage of the lesion from a small window with removal of the lesion followed by injectable phosphocalcic cement application with autologous PRP can be considered as a curative and technically simple treatment method.

Does diabetes affect the distribution and number of interstitial cells and neuronal tissue in the ureter, bladder, prostate, and urethra of humans?

INTRODUCTION: The aim of this study was to investigate and compare the distribution and number of interstitial cells (ICs) and neuronal tissue in the ureter, bladder, prostate, and urethra of human patients with and without diabetes. MATERIAL AND METHODS: Human tissue was obtained from patients who had undergone radical cystectomy for bladder cancer (10 diabetic and 11 non-diabetic males). Interstitial cells were stained immunohistochemically with anti-human CD117 (c-kit) rabbit polyclonal antibody, Vimentin, and Connexin-43. Neural tissue was stained with synaptophysin. The number of ICs and neurons was evaluated and compared between the groups (diabetic versus non-diabetic). RESULTS: The mean number of c-kit (+) ICs in bladder lamina propria was significantly decreased in diabetics (32.40 ±12.96 versus 57.18 ±25.37, p = 0.036). The mean number of ICs in the detrusor muscle was significantly decreased in diabetics (40.50 ±16.79 versus 64.55 ±22.08, p = 0.013). Between the groups, no significant differences were detected regarding the number of ICs at the level of the ureter, urethra, and prostate. No significant differences were detected regarding the number of nerves in the ureter, bladder, prostate, and urethra of both groups. CONCLUSIONS: The number of ICs may be decreased in the lamina propria and detrusor muscle of the human bladder in diabetes. This can be an underlying cause of lower urinary tract (LUT) dysfunction in diabetics. Research into the development of drugs targeting or stimulating IC function in order to prevent diabetic LUT dysfunction is warranted.

Obstructive fibrinous tracheal pseudomembrane.

Obstructive fibrinous tracheal pseudomembrane is a rare but potentially fatal complication associated with endotracheal intubation. Little is known about the mechanisms that play a role in the development of tracheal pseudomembrane, but it requires early diagnosis and treatment to prevent its major consequences. In this report, we present a case of obstructive fibrinous tracheal pseudomembrane, which developed a day after extubation in a patient who was intubated for 2 days. Therapeutic bronchoscopy was highly successful in removing the lesion and improving the clinical course.

A rare sinonasal neoplasm: fibrosarcoma.

Sinonasal fibrosarcoma is an infrequently occurring malignant neoplasm. It usually presents with nasal obstruction and epistaxis, as do other sarcomas in this region. The final diagnosis is based on the histopathologic and immunohistochemical examination. We report a case involving a 47-year-old woman with a 2-year history of left nasal obstruction and proptosis, as well as diplopia for the 2 months preceding her visit. Computed tomography and magnetic resonance imaging showed a neoplasm occupying the left nasal cavity, ethmoid sinuses, and bilateral frontal sinuses. The neoplasm also was eroding the medial wall of the maxillary sinus, the lamina papyracea, the cribriform plate, and the anterior wall of the frontal sinus. Complete removal of the tumor was achieved both endoscopically and through a Lynch incision. Sinonasal fibrosarcoma was found on histopathologic examination.